Wikiversity

PLOS/Origins of DNA Replication

< PLOS

PLOS Topic Pages
PLOS Computational Biology • PLOS Genetics • PLOS ONE

OPEN ACCESS (CC BY 4.0)

This article has been published as a PLOS Topic Page

Published in PLOS Genetics
Adapted for English Wikipedia
Public peer review comments can be seen here
Published under Creative Commons License CC BY 4.0
10.1371/journal.pgen.1008320


Authors
Babatunde Ekundayo, Franziska Bleichert
About the Authors 

Babatunde Ekundayo
AFFILIATION: Friedrich Miescher Institute for Biomedical Research , 4058 Basel, Switzerland

Franziska Bleichert
AFFILIATION: Friedrich Miescher Institute for Biomedical Research , 4058 Basel, Switzerland
0000-0003-0014-770X


Abstract

edit

In all kingdoms of life, DNA is used to encode hereditary information. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. DNA synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Here, we discuss commonalities and differences in replication origin organization and recognition in the three domains of life.


Introduction

edit
 
Models for bacterial (A) and eukaryotic (B) DNA replication initiation. A) Circular bacterial chromosomes contain a cis-acting element, the replicator, that is located at or near replication origins. i) The replicator recruits initiator proteins in a DNA sequence-specific manner, which results in melting of the DNA helix and loading of the replicative helicase onto each of the single DNA strands (ii). iii) Assembled replisomes bidirectionally replicate DNA to yield two copies of the bacterial chromosome. B) Linear eukaryotic chromosomes contain many replication origins. Initiator binding (i) facilitates replicative helicase loading (ii) onto duplex DNA to license origins. iii) A subset of loaded helicases is activated for replisome assembly. Replication proceeds bidirectionally from origins and terminates when replication forks from adjacent active origins meet (iv).

In the second half of the 19th century, Gregor Mendel's pioneering work on the inheritance of traits in pea plants suggested that specific “factors” (today established as genes) are responsible for transferring organismal traits between generations.[1] Although proteins were initially assumed to serve as the hereditary material, Avery, MacLeod and McCarty established a century later DNA, which had been discovered by Friedrich Miescher, as the carrier of genetic information.[2] These findings paved the way for research uncovering the chemical nature of DNA and the rules for encoding genetic information, and ultimately led to the proposal of the double-helical structure of DNA by Watson and Crick.[3] This three-dimensional model of DNA illuminated potential mechanisms by which the genetic information could be copied in a semiconservative manner prior to cell division, a hypothesis that was later experimentally supported by Meselson and Stahl using isotope incorporation to distinguish parental from newly synthesized DNA.[4][5] The subsequent isolation of DNA polymerases, the enzymes that catalyze the synthesis of new DNA strands, by Kornberg and colleagues pioneered the identification of many different components of the biological DNA replication machinery, first in the bacterial model organism E. coli, but later also in eukaryotic life forms.[6]

A key prerequisite for DNA replication is that it must occur with extremely high fidelity and efficiency exactly once per cell cycle to prevent the accumulation of genetic alterations with potentially deleterious consequences for cell survival and organismal viability.[7] Incomplete, erroneous, or untimely DNA replication events can give rise to mutations, chromosomal polyploidy or aneuploidy, and gene copy number variations, each of which in turn can lead to diseases, including cancer.[8][9] To ensure complete and accurate duplication of the entire genome and the correct flow of genetic information to progeny cells, all DNA replication events are not only tightly regulated with cell cycle cues but are also coordinated with other cellular events such as transcription and DNA repair.[10][11][12]

DNA replication is divided into different stages (Figure 1). During initiation, the replication machineries – termed replisomes – are assembled on DNA in a bidirectional fashion. These assembly loci constitute the start sites of DNA replication or replication origins. In the elongation phase, replisomes travel in opposite directions with the replication forks, unwinding the DNA helix and synthesizing complementary daughter DNA strands using both parental strands as templates. Once replication is complete, specific termination events lead to the disassembly of replisomes. As long as the entire genome is duplicated before cell division, one might assume that the location of replication start sites does not matter; yet, it has been shown that many organisms use preferred genomic regions as origins.[13][14] The necessity to regulate origin location likely arises from the need to coordinate DNA replication with other processes that act on the shared chromatin template to avoid DNA strand breaks and DNA damage.[8][12][15][16][17][18][19]

The Replicon Model

edit

More than five decades ago, Jacob, Brenner, and Cuzin proposed the replicon hypothesis to explain the regulation of chromosomal DNA synthesis in E. coli.[20] The model postulates that a diffusible, trans-acting factor, a so-called initiator, interacts with a cis-acting DNA element, the replicator, to promote replication onset at a nearby origin (Figure 1A, i). Once bound to replicators, initiators (often with the help of co-loader proteins) deposit replicative helicases onto DNA, which subsequently drive the recruitment of additional replisome components and the assembly of the entire replication machinery (Figure 1A, ii). The replicator thereby specifies the location of replication initiation events, and the chromosome region that is replicated from a single origin or initiation event is defined as the replicon.

A fundamental feature of the replicon hypothesis is that it relies on positive regulation to control DNA replication onset, which can explain many experimental observations in bacterial and phage systems.[20] For example, it accounts for the failure of extrachromosomal DNAs without origins to replicate when introduced into host cells. It further rationalizes plasmid incompatibilities in E. coli, where certain plasmids destabilize each other’s inheritance due to competition for the same molecular initiation machinery.[21] By contrast, a model of negative regulation (analogous to the replicon-operator model for transcription) fails to explain the above findings.[20] Nonetheless, research subsequent to Jacob’s, Brenner’s and Cuzin’s proposal of the replicon model has discovered many additional layers of replication control in bacteria and eukaryotes that comprise both positive and negative regulatory elements, highlighting both the complexity and the importance of restricting DNA replication temporally and spatially.[22][23][24]

The concept of the replicator as a genetic entity has proven very useful in the quest to identify replicator DNA sequences and initiator proteins in prokaryotes, and to some extent also in eukaryotes, although the organization and complexity of replicators differ considerably between the domains of life (for reviews, see [25][26]). While bacterial genomes typically contain a single replicator that is specified by consensus DNA sequence elements and that controls replication of the entire chromosome (Figure 1A), most eukaryotic replicators – with the exception of budding yeast – are not defined at the level of DNA sequence; instead, they appear to be specified combinatorially by local DNA structural and chromatin cues.[27][28][29][30][31][32][33][34][35][36] Eukaryotic chromosomes are also much larger than their bacterial counterparts, raising the need for initiating DNA synthesis from many origins simultaneously to ensure timely replication of the entire genome (Figure 1B). Additionally, many more replicative helicases are loaded than activated to initiate replication in a given cell cycle (Figure 1B). The context-driven definition of replicators and selection of origins suggests a relaxed replicon model in eukaryotic systems that allows for flexibility in the DNA replication program.[25] Although replicators and origins can be spaced physically apart on chromosomes, they often co-localize or are located in close proximity; for simplicity, we will thus refer to both elements as ‘origins’ throughout this review. Taken together, the discovery and isolation of origin sequences in various organisms represents a significant milestone towards gaining mechanistic understanding of replication initiation. In addition, these accomplishments had profound biotechnological implications for the development of shuttle vectors that can be propagated in bacterial, yeast and mammalian cells.[37][38][39]

Bacterial Replication Origins

edit
 
Origin organization and recognition in bacteria. A) Schematic of the architecture of E. coli origin oriC, Thermotoga maritima oriC, and the bipartite origin in Helicobacter pylori. The DUE is flanked on one side by several high- and weak-affinity DnaA-boxes as indicated for E. coli oriC. B) Domain organization of the E. coli initiator DnaA. Magenta circle indicates the single-strand DNA binding site. C) Models for origin recognition and melting by DnaA. In the two-state model (left panel), the DnaA protomers transition from a dsDNA binding mode (mediated by the HTH-domains recognizing DnaA-boxes) to an ssDNA binding mode (mediated by the AAA+ domains). In the loop-back model, the DNA is sharply bent backwards onto the DnaA filament (facilitated by the regulatory protein IHF[40]) so that a single protomer binds both duplex and single-stranded regions. In either instance, the DnaA filament melts the DNA duplex and stabilizes the initiation bubble prior to loading of the replicative helicase (DnaB in E. coli). HTH – helix-turn-helix domain, DUE – DNA unwinding element, IHF – integration host factor.

Most bacterial chromosomes are circular and contain a single origin of chromosomal replication (oriC). Bacterial oriC regions are surprisingly diverse in size (ranging from 250 bp to 2 kbp), sequence, and organization;[41][42] nonetheless, their ability to drive replication onset typically depends on sequence-specific readout of consensus DNA elements by the bacterial initiator, a protein called DnaA.[43][44][45][46] Origins in bacteria are either continuous or bipartite and contain three functional elements that control origin activity: conserved DNA repeats that are specifically recognized by DnaA (called DnaA-boxes), an AT-rich DNA unwinding element (DUE), and binding sites for proteins that help regulate replication initiation (for reviews, see [13][47][48]; Figure 2A). Interactions of DnaA both with the double-stranded (ds) DnaA-box regions and with single-stranded (ss) DNA in the DUE are important for origin activation and are mediated by different domains in the initiator protein: a helix-turn-helix (HTH) DNA binding element and an ATPase associated with various cellular activities (AAA+) domain, respectively (Figure 2B).[49][50][51][52][53][54][55][56] While the sequence, number, and arrangement of origin-associated DnaA-boxes vary throughout the bacterial kingdom, their specific positioning and spacing in a given species are critical for oriC function and for productive initiation complex formation.[41][42][57][58][59][60][61]

Among bacteria, E. coli is a particularly powerful model system to study the organization, recognition, and activation mechanism of replication origins. E. coli oriC comprises an approximately ~260 bp region containing four types of initiator binding elements that differ in their affinities for DnaA and their dependencies on the co-factor ATP (Figure 2A). DnaA-boxes R1, R2, and R4 constitute high-affinity sites that are bound by the HTH domain of DnaA irrespective of the nucleotide-binding state of the initiator.[43][62][63][64][65][66] By contrast, the I, τ, and C-sites, which are interspersed between the R-sites, are low-affinity DnaA-boxes and associate preferentially with ATP-bound DnaA, although ADP-DnaA can substitute for ATP-DnaA under certain conditions.[67][68][69][60] Binding of the HTH domains to the high- and low-affinity DnaA recognition elements promotes ATP-dependent higher-order oligomerization of DnaA’s AAA+ modules into a right-handed filament that wraps duplex DNA around its outer surface, thereby generating superhelical torsion that facilitates melting of the adjacent AT-rich DUE (Figure 2C).[49][70][71][72] DNA strand separation is additionally aided by direct interactions of DnaA’s AAA+ ATPase domain with triplet repeats, so-called DnaA-trios, in the proximal DUE region.[73] The engagement of single-stranded trinucleotide segments by the initiator filament stretches DNA and stabilizes the initiation bubble by preventing reannealing.[53] The DnaA-trio origin element is conserved in many bacterial species, indicating it is a key element for origin function.[73] After melting, the DUE provides an entry site for the E. coli replicative helicase DnaB, which is deposited onto each of the single DNA strands by its loader protein DnaC .

Although the different DNA binding activities of DnaA have been extensively studied biochemically and various apo, ssDNA-, or dsDNA-bound structures have been determined,[52][53][54][71] the exact architecture of the higher-order DnaA-oriC initiation assembly remains unclear. Two models have been proposed to explain the organization of essential origin elements and DnaA-mediated oriC melting. The two-state model assumes a continuous DnaA filament that switches from a dsDNA binding mode (the organizing complex) to an ssDNA binding mode in the DUE (the melting complex) (Figure 2C, left panel).[71][74] By contrast, in the loop-back model, the DNA is sharply bent in oriC and folds back onto the initiator filament so that DnaA protomers simultaneously engage double- and single-stranded DNA regions (Figure 2C, right panel).[75] Elucidating how exactly oriC DNA is organized by DnaA remains thus an important task for future studies. Insights into initiation complex architecture will help explain not only how origin DNA is melted, but also how a replicative helicase is loaded directionally onto each of the exposed single DNA strands in the unwound DUE, and how these events are aided by interactions of the helicase with the initiator and specific loader proteins.

Archaeal Replication Origins

edit
 
Origin organization and recognition in archaea. A) The circular chromosome of Sulfolobus solfataricus contains three different origins. B) Arrangement of initiator binding sites at two S. solfataricus origins, oriC1 and oriC2. Orc1-1 association with ORB elements is shown for oriC1. Recognition elements for additional Orc1/Cdc6 paralogs are also indicated, while WhiP binding sites have been omitted. C) Domain architecture of archaeal Orc1/Cdc6 paralogs. The orientation of ORB elements at origins leads to directional binding of Orc1/Cdc6 and MCM loading in between opposing ORBs (in B). (m)ORB – (mini-)origin recognition box, DUE – DNA unwinding element, WH – winged-helix domain.

Archaeal replication origins share some but not all of the organizational features of bacterial oriC. Unlike bacteria, archaea often initiate replication from multiple origins per chromosome (one to four have been reported);[76][77][78][79][80][81][82][83][42] yet, archaeal origins also bear specialized sequence regions that control origin function (for recent reviews, see [84][85][86]). These elements include both DNA sequence-specific origin recognition boxes (ORBs or miniORBs) and an AT-rich DUE that is flanked by one or several ORB regions.[82][87] ORB elements display a considerable degree of diversity in terms of their number, arrangement, and sequence, both among different archaeal species and among different origins within in a single species.[77][82][88] An additional degree of complexity is introduced by the initiator, Orc1/Cdc6 in archaea, which binds to ORB regions. Archaeal genomes typically encode multiple paralogs of Orc1/Cdc6 that vary substantially in their affinities for distinct ORB elements and that differentially contribute to origin activities.[82][89][90][91] In Sulfolobus solfataricus, for example, three chromosomal origins have been mapped (oriC1, oriC2, and oriC3; Figure 3A), and biochemical studies have revealed complex binding patterns of initiators at these sites (Figure 3B).[82][83][92][93] The cognate initiator for oriC1 is Orc1-1, which associates with several ORBs at this origin.[82][90] OriC2 and oriC3 are bound by both Orc1-1 and Orc1-3.[82][90][93] Conversely, a third paralog, Orc1-2, footprints at all three origins but has been postulated to negatively regulate replication initiation.[82][93] Additionally, the WhiP protein, an initiator unrelated to Orc1/Cdc6, has been shown to bind all origins as well and to drive origin activity of oriC3 in the closely related Sulfolobus islandicus.[90][92] Because archaeal origins often contain several adjacent ORB elements, multiple Orc1/Cdc6 paralogs can be simultaneously recruited to an origin and oligomerize in some instances;[91][94] however, in contrast to bacterial DnaA, formation of a higher-order initiator assembly does not appear to be a general prerequisite for origin function in the archaeal domain.

Structural studies have provided insights into how archaeal Orc1/Cdc6 recognizes ORB elements and remodels origin DNA.[94][95] Orc1/Cdc6 paralogs are two-domain proteins and are composed of a AAA+ ATPase module fused to a C-terminal winged-helix fold (Figure 3C).[96][97][98] DNA-complexed structures of Orc1/Cdc6 revealed that ORBs are bound by an Orc1/Cdc6 monomer despite the presence of inverted repeat sequences within ORB elements.[94][95] Both the ATPase and winged-helix regions interact with the DNA duplex but contact the palindromic ORB repeat sequence asymmetrically, which orients Orc1/Cdc6 in a specific direction on the repeat.[94][95] Interestingly, the DUE-flanking ORB or miniORB elements often have opposite polarities,[77][82][91][99][100] which predicts that the AAA+ lid subdomains and the winged-helix domains of Orc1/Cdc6 are positioned on either side of the DUE in a manner where they face each other (Figure 3B, bottom panel).[94][95] Since both regions of Orc1/Cdc6 associate with a minichromosome maintenance (MCM) replicative helicase,[101][102] this specific arrangement of ORB elements and Orc1/Cdc6 is likely important for loading two MCM complexes symmetrically onto the DUE (Figure 3B).[82] Surprisingly, while the ORB DNA sequence determines the directionality of Orc1/Cdc6 binding, the initiator makes relatively few sequence-specific contacts with DNA.[94][95] However, Orc1/Cdc6 severely underwinds and bends DNA, suggesting that it relies on a mix of both DNA sequence and context-dependent DNA structural features to recognize origins.[94][95][103] Notably, base pairing is maintained in the distorted DNA duplex upon Orc1/Cdc6 binding in the crystal structures,[94][95] whereas biochemical studies have yielded contradictory findings as to whether archaeal initiators can melt DNA similarly to bacterial DnaA.[90][91][104] Although the evolutionary kinship of archaeal and eukaryotic initiators and replicative helicases indicates that archaeal MCM is likely loaded onto duplex DNA (see next section), the temporal order of origin melting and helicase loading, as well as the mechanism for origin DNA melting, in archaeal systems remains therefore to be clearly established. Likewise, how exactly the MCM helicase is loaded onto DNA needs to be addressed in future studies.

Eukaryotic Replication Origins

edit
 
Origin organization and recognition in eukaryotes. Specific DNA elements and epigenetic features involved in ORC recruitment and origin function are summarized for S. cerevisiae, S. pombe, and metazoan origins. A schematic of the ORC architecture is also shown, highlighting the arrangement of the AAA+ and winged-helix domains into a pentameric ring that encircles origin DNA. Ancillary domains of several ORC subunits involved in targeting ORC to origins are included. Other regions in ORC subunits may also be involved in initiator recruitment, either by directly or indirectly associating with partner proteins. A few examples are listed. Note that the BAH domain in S. cerevisiae Orc1 binds nucleosomes[105] but does not recognize H4K20me2.[106] BAH – bromo-adjacent homology domain, WH – winged-helix domain, TFIIB – transcription factor II B-like domain in Orc6, G4 – G quadruplex, OGRE – origin G-rich repeated element.

Origin organization, specification, and activation in eukaryotes are more complex than in bacterial or archaeal kingdoms and significantly deviate from the paradigm established for prokaryotic replication initiation. The large genome sizes of eukaryotic cells, which range from 12 Mbp in S. cerevisiae to 3 Gbp in humans, necessitates that DNA replication starts at several hundred (in budding yeast) to tens of thousands (in humans) origins to complete DNA replication of all chromosomes during each cell cycle (for recent reviews, see [32][23]). With the exception of S. cerevisiae and related Saccharomycotina species, eukaryotic origins do not contain consensus DNA sequence elements but their location is influenced by contextual cues such as local DNA topology, DNA structural features, and chromatin environment.[25][31][33] Nonetheless, eukaryotic origin function still relies on a conserved initiator protein complex to load replicative helicases onto DNA during the late M and G1 phases of the cell cycle, a step known as origin licensing (Figure 1B).[107] In contrast to their bacterial counterparts, replicative helicases in eukaryotes are loaded onto origin duplex DNA in an inactive, double-hexameric form and only a subset of them (10-20% in mammalian cells) is activated during any given S phase, events that are referred to as origin firing (Figure 1B).[108][109][110] The location of active eukaryotic origins is therefore determined on at least two different levels, origin licensing to mark all potential origins, and origin firing to select a subset that permits assembly of the replication machinery and initiation of DNA synthesis. The extra licensed origins serve as backup and are activated only upon slowing or stalling of nearby replication forks, ensuring that DNA replication can be completed when cells encounter replication stress.[111][112] Together, the excess of licensed origins and the tight cell cycle control of origin licensing and firing embody two important strategies to prevent under- and overreplication and to maintain the integrity of eukaryotic genomes.

Early studies in S. cerevisiae indicated that replication origins in eukaryotes might be recognized in a DNA-sequence-specific manner analogously to those in prokaryotes. In budding yeast, the search for genetic replicators lead to the identification of autonomously replicating sequences (ARS) that support efficient DNA replication initiation of extrachromosomal DNA.[113][114][115] These ARS regions are approximately 100-200 bp long and exhibit a multipartite organization, containing A, B1, B2, and sometimes B3 elements that together are essential for origin function (Figure 4).[116][117] The A element encompasses the conserved 11 bp ARS consensus sequence (ACS),[118][119] which, in conjunction with the B1 element, constitutes the primary binding site for the heterohexameric origin recognition complex (ORC), the eukaryotic replication initiator.[120][121][122][123] Within ORC, five subunits are predicated on conserved AAA+ ATPase and winged-helix folds and co-assemble into a pentameric ring that encircles DNA (Figure 4).[123][124][125] In budding yeast ORC, DNA binding elements in the ATPase and winged-helix domains, as well as adjacent basic patch regions in some of the ORC subunits, are positioned in the central pore of the ORC ring such that they aid the DNA-sequence-specific recognition of the ACS in an ATP-dependent manner.[123][126] By contrast, the roles of the B2 and B3 elements are less clear. The B2 region is similar to the ACS in sequence and has been suggested to function as a second ORC binding site under certain conditions, or as a binding site for the replicative helicase core.[127][128][129][130][131] Conversely, the B3 element recruits the transcription factor Abf1, albeit B3 is not found at all budding yeast origins and Abf1 binding does not appear to be strictly essential for origin function.[116][132][133]

Origin recognition in eukaryotes other than S. cerevisiae or its close relatives does not conform to the sequence-specific read-out of conserved origin DNA elements. Pursuits to isolate specific chromosomal replicator sequences more generally in eukaryotic species, either genetically or by genome-wide mapping of initiator binding or replication start sites, have failed to identify clear consensus sequences at origins.[134][135][136][137][138][139][140][141][142][143][144][145] Thus, sequence-specific DNA-initiator interactions in budding yeast signify a specialized mode for origin recognition in this system rather than an archetypal mode for origin specification across the eukaryotic domain. Nonetheless, DNA replication does initiate at discrete sites that are not randomly distributed across eukaryotic genomes, arguing that alternative means determine the chromosomal location of origins in these systems. These mechanisms involve a complex interplay between DNA accessibility, nucleotide sequence skew (both AT-richness and CpG islands have been linked to origins), nucleosome positioning, epigenetic features, DNA topology and certain DNA structural features (e.g., G4 motifs), as well as regulatory proteins and transcriptional interference.[13][14][30][31][33] [146][147][139][148] Importantly, origin properties vary not only between different origins in an organism and among species, but some can also change during development and cell differentiation. The chorion locus in Drosophila follicle cells constitutes a well-established example for spatial and developmental control of initiation events. This region undergoes DNA-replication-dependent gene amplification at a defined stage during oogenesis and relies on the timely and specific activation of chorion origins, which in turn is regulated by origin-specific cis-elements and several protein factors, including the Myb complex, E2F1, and E2F2.[149][150][151][152][153] This combinatorial specification and multifactorial regulation of metazoan origins has complicated the identification of unifying features that determine the location of replication start sites across eukaryotes more generally.

To facilitate replication initiation and origin recognition, ORC assemblies from various species have evolved specialized auxiliary domains that are thought to aid initiator targeting to chromosomal origins or chromosomes in general (Figure 4). For example, the Orc4 subunit in S. pombe ORC contains several AT-hooks that preferentially bind AT-rich DNA,[154] while in metazoan ORC the TFIIB-like domain of Orc6 is thought to perform a similar function.[155] Metazoan Orc1 proteins also harbor a bromo-adjacent homology (BAH) domain that interacts with H4K20me2-nucleosomes.[106] Particularly in mammalian cells, H4K20 methylation has been reported to be required for efficient replication initiation, and the Orc1-BAH domain facilitates ORC association with chromosomes and Epstein-Barr virus origin-dependent replication.[156][157][158][159][160] Therefore, it is intriguing to speculate that both observations are mechanistically linked at least in a subset of metazoa, but this possibility needs to be further explored in future studies. In addition to the recognition of certain DNA or epigenetic features, ORC also associates directly or indirectly with several partner proteins that could aid initiator recruitment, including LRWD1, PHIP (or DCAF14), HMGA1a, among others (Figure 4).[29][161][162][163][164][165][166][167] Interestingly, Drosophila ORC, like its budding yeast counterpart, bends DNA and negative supercoiling has been reported to enhance DNA binding of this complex, suggesting that DNA shape and malleability might influence the location of ORC binding sites across metazoan genomes.[27][123][168][169][170] A molecular understanding for how ORC’s DNA binding regions might support the read out of structural properties of the DNA duplex in metazoans rather than of specific DNA sequences as in S. cerevisiae awaits high-resolution structural information of DNA-bound metazoan initiator assemblies. Likewise, whether and how different epigenetic factors contribute to initiator recruitment in metazoan systems is poorly defined and is an important question that needs to be addressed in more detail.

Once recruited to origins, ORC and its co-factors Cdc6 and Cdt1 drive the deposition of the minichromosome maintenance 2-7 (Mcm2-7) complex onto DNA (for reviews see [107][171]). Like the archaeal replicative helicase core, Mcm2-7 is loaded as a head-to-head double hexamer onto DNA to license origins (Figure 1B).[108][109][110] In S-phase, Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) phosphorylate several Mcm2-7 subunits and additional initiation factors to promote the recruitment of the helicase co-activators Cdc45 and GINS, DNA melting, and ultimately bidirectional replisome assembly at a subset of the licensed origins (Figure 1B).[172][24] In both yeast and metazoans, origins are free or depleted of nucleosomes, a property that is crucial for Mcm2-7 loading, indicating that chromatin state at origins regulates not only initiator recruitment but also helicase loading.[140][173][174][175][176][177] A permissive chromatin environment is further important for origin activation and has been implicated in regulating both origin efficiency and the timing of origin firing. Euchromatic origins typically contain active chromatin marks, replicate early, and are more efficient than late-replicating, heterochromatic origins, which conversely are characterized by repressive marks.[23][175][178] Not surprisingly, several chromatin remodelers and chromatin-modifying enzymes have been found to associate with origins and certain initiation factors,[179][180] but how their activities impact different replication initiation events remains largely obscure. Remarkably, cis-acting “early replication control elements” (ECREs) have recently also been identified to help regulate replication timing and to influence 3D genome architecture in mammalian cells.[181] Understanding the molecular and biochemical mechanisms that orchestrate this complex interplay between 3D genome organization, local and higher-order chromatin structure, and replication initiation is an exciting topic for further studies.

Why have metazoan replication origins diverged from the DNA sequence-specific recognition paradigm that determines replication start sites in prokaryotes and budding yeast? Observations that metazoan origins often co-localize with promoter regions in Drosophila and mammalian cells and that replication-transcription conflicts due to collisions of the underlying molecular machineries can lead to DNA damage suggest that proper coordination of transcription and replication is important for maintaining genome stability.[135][137][139][142][182][16][17][19] Recent findings also point to a more direct role of transcription in influencing the location of origins, either by inhibiting Mcm2-7 loading or by repositioning of loaded Mcm2-7 on chromosomes.[183][148] Sequence-independent (but not necessarily random) initiator binding to DNA additionally allows for flexibility in specifying helicase loading sites and, together with transcriptional interference and the variability in activation efficiencies of licensed origins, likely determines origin location and contributes to the co-regulation of DNA replication and transcriptional programs during development and cell fate transitions. Computational modeling of initiation events in S. pombe, as well as the identification of cell-type specific and developmentally-regulated origins in metazoans, are in agreement with this notion.[136][144][184][185][186][187][188][148] However, a large degree of flexibility in origin choice also exists among different cells within a single population,[139][145][185] albeit the molecular mechanisms that lead to the heterogeneity in origin usage remain ill-defined. Mapping origins in single cells in metazoan systems and correlating these initiation events with single-cell gene expression and chromatin status will be important to elucidate whether origin choice is purely stochastic or controlled in a defined manner.

Concluding Remarks

edit

Although DNA replication is essential for genetic inheritance, defined, site-specific replication origins are technically not a requirement for genome duplication as long as all chromosomes are copied in their entirety to maintain gene copy numbers. Certain bacteriophages and viruses, for example, can initiate DNA replication by homologous recombination independent of dedicated origins.[189] Likewise, the archaeon Haloferax volcanii uses recombination-dependent initiation to duplicate its genome when its endogenous origins are deleted.[78] Similar non-canonical initiation events through break-induced or transcription-initiated replication have been reported in E. coli and S. cerevisiae.[190][191][192][193][194] Nonetheless, despite the ability of cells to sustain viability under these exceptional circumstances, origin-dependent initiation is a common strategy universally adopted across different domains of life. The controlled assembly of the replication machinery at origins likely confers long-term advantage to cells by allowing tight cell cycle regulation and by maintaining a specific replication dynamics. The divergent origin specification modes between prokaryotes and budding yeast on the one hand and metazoans on the other hand appear to reflect distinct needs to coordinate the spatiotemporal replication program with gene expression and cell differentiation programs to ensure not only genetic but also epigenetic inheritance and to preserve cell identity. Deciphering the underlying molecular mechanisms that modulate origin location, usage, and timing to define the replication program in metazoan systems represents an important major challenge in the field and will be essential to understand how dysregulation of these events are linked to human diseases. In addition, detailed studies of replication initiation have focused on a limited number of model systems. The extensively studied fungi and metazoa are both members of the opisthokont supergroup and exemplify only a small fraction of the evolutionary landscape in the eukaryotic domain.[195] Comparably few efforts have been directed at other eukaryotic model systems, such as kinetoplastids or tetrahymena.[196][197][198][199][200][201][202] Surprisingly, these studies have revealed interesting differences both in origin properties and in initiator composition compared to yeast and metazoans. Further exploration of replication initiation mechanisms across different branches of the eukaryotic domain will likely yield unexpected insight into the diversity and evolution of this fundamental biological process.


References

edit
  1. ↑ Mendel G (1865) Versuche ueber Pflanzenhybriden Verhandlungen des naturforschenden Vereines in Bruenn, Bd IV Abhandlungen:3-47
  2. ↑ Avery, O. T.; MacLeod, C. M.; McCarty, M. (1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types : Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". The Journal of Experimental Medicine 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMID 19871359. PMC 2135445. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445/. 
  3. ↑ WATSON JD; CRICK FH (1953). "The structure of DNA". Cold Spring Harbor Symposia on Quantitative Biology 18: 123–131. doi:10.1101/sqb.1953.018.01.020. PMID 13168976. 
  4. ↑ Meselson, M.; Stahl, F. W. (1958). "The Replication of DNA in Escherichia Coli". Proceedings of the National Academy of Sciences of the United States of America 44 (7): 671–682. doi:10.1073/pnas.44.7.671. PMID 16590258. PMC 528642. //www.ncbi.nlm.nih.gov/pmc/articles/PMC528642/. 
  5. ↑ MESELSON M; STAHL FW (1958). "The replication of DNA". Cold Spring Harbor Symposia on Quantitative Biology 23: 9–12. doi:10.1101/sqb.1958.023.01.004. PMID 13635537. 
  6. ↑ LEHMAN IR; BESSMAN MJ; SIMMS ES; KORNBERG A (1958). "Enzymatic synthesis of deoxyribonucleic acid. I. Preparation of substrates and partial purification of an enzyme from Escherichia coli". The Journal of Biological Chemistry 233 (1): 163–170. doi:10.1016/S0021-9258(19)68048-8. PMID 13563462. 
  7. ↑ O'Donnell, M.; Langston, L.; Stillman, B. (2013). "Principles and concepts of DNA replication in bacteria, archaea, and eukarya". Cold Spring Harbor Perspectives in Biology 5 (7): a010108. doi:10.1101/cshperspect.a010108. PMID 23818497. PMC 3685895. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3685895/. 
  8. ↑ 8.0 8.1 Barlow, J. H.; Nussenzweig, A. (2014). "Replication initiation and genome instability: A crossroads for DNA and RNA synthesis". Cellular and Molecular Life Sciences : CMLS 71 (23): 4545–4559. doi:10.1007/s00018-014-1721-1. PMID 25238783. PMC 6289259. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6289259/. 
  9. ↑ Abbas, T.; Keaton, M. A.; Dutta, A. (2013). "Genomic instability in cancer". Cold Spring Harbor Perspectives in Biology 5 (3): a012914. doi:10.1101/cshperspect.a012914. PMID 23335075. PMC 3578360. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3578360/. 
  10. ↑ Siddiqui, K.; On, K. F.; Diffley, J. F. (2013). "Regulating DNA replication in eukarya". Cold Spring Harbor Perspectives in Biology 5 (9): a012930. doi:10.1101/cshperspect.a012930. PMID 23838438. PMC 3753713. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3753713/. 
  11. ↑ Sclafani, R. A.; Holzen, T. M. (2007). "Cell cycle regulation of DNA replication". Annual Review of Genetics 41: 237–280. doi:10.1146/annurev.genet.41.110306.130308. PMID 17630848. PMC 2292467. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2292467/. 
  12. ↑ 12.0 12.1 García-Muse, T.; Aguilera, A. (2016). "Transcription-replication conflicts: How they occur and how they are resolved". Nature Reviews. Molecular Cell Biology 17 (9): 553–563. doi:10.1038/nrm.2016.88. PMID 27435505. 
  13. ↑ 13.0 13.1 13.2 Leonard, A. C.; Méchali, M. (2013). "DNA replication origins". Cold Spring Harbor Perspectives in Biology 5 (10): a010116. doi:10.1101/cshperspect.a010116. PMID 23838439. PMC 3783049. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3783049/. 
  14. ↑ 14.0 14.1 Creager, R. L.; Li, Y.; MacAlpine, D. M. (2015). "SnapShot: Origins of DNA replication". Cell 161 (2): 418–418.e1. doi:10.1016/j.cell.2015.03.043. PMID 25860614. 
  15. ↑ Knott, S. R.; Viggiani, C. J.; Aparicio, O. M. (2009). "To promote and protect: Coordinating DNA replication and transcription for genome stability". Epigenetics 4 (6): 362–365. doi:10.4161/epi.4.6.9712. PMID 19736523. 
  16. ↑ 16.0 16.1 Deshpande, A. M.; Newlon, C. S. (1996). "DNA replication fork pause sites dependent on transcription". Science 272 (5264): 1030–1033. doi:10.1126/science.272.5264.1030. PMID 8638128. 
  17. ↑ 17.0 17.1 Sankar, T. S.; Wastuwidyaningtyas, B. D.; Dong, Y.; Lewis, S. A.; Wang, J. D. (2016). "The nature of mutations induced by replication–transcription collisions". Nature 535 (7610): 178–181. doi:10.1038/nature18316. PMID 27362223. PMC 4945378. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4945378/. 
  18. ↑ Liu, B.; Alberts, B. M. (1995). "Head-on collision between a DNA replication apparatus and RNA polymerase transcription complex". Science 267 (5201): 1131–1137. doi:10.1126/science.7855590. PMID 7855590. 
  19. ↑ 19.0 19.1 Azvolinsky, A.; Giresi, P. G.; Lieb, J. D.; Zakian, V. A. (2009). "Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae". Molecular Cell 34 (6): 722–734. doi:10.1016/j.molcel.2009.05.022. PMID 19560424. PMC 2728070. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2728070/. 
  20. ↑ 20.0 20.1 20.2 Jacob F, Brenner S & Cuzin F (1963) On the regulation of DNA replication in bacteria Cold Spring Harbor Symp Quant Biol 28:329-48
  21. ↑ Novick, R. P. (1987). "Plasmid incompatibility". Microbiological Reviews 51 (4): 381–395. doi:10.1128/mr.51.4.381-395.1987. PMID 3325793. PMC 373122. //www.ncbi.nlm.nih.gov/pmc/articles/PMC373122/. 
  22. ↑ Skarstad, K.; Katayama, T. (2013). "Regulating DNA replication in bacteria". Cold Spring Harbor Perspectives in Biology 5 (4): a012922. doi:10.1101/cshperspect.a012922. PMID 23471435. PMC 3683904. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3683904/. 
  23. ↑ 23.0 23.1 23.2 Marks, A. B.; Fu, H.; Aladjem, M. I. (2017). "Regulation of Replication Origins". Advances in Experimental Medicine and Biology 1042: 43–59. doi:10.1007/978-981-10-6955-0_2. ISBN 978-981-10-6954-3. PMID 29357052. PMC 6622447. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6622447/. 
  24. ↑ 24.0 24.1 Parker, M. W.; Botchan, M. R.; Berger, J. M. (2017). "Mechanisms and regulation of DNA replication initiation in eukaryotes". Critical Reviews in Biochemistry and Molecular Biology 52 (2): 107–144. doi:10.1080/10409238.2016.1274717. PMID 28094588. PMC 5545932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5545932/. 
  25. ↑ 25.0 25.1 25.2 Gilbert, D. M. (2004). "In search of the holy replicator". Nature Reviews. Molecular Cell Biology 5 (10): 848–855. doi:10.1038/nrm1495. PMID 15459665. PMC 1255919. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1255919/. 
  26. ↑ Aladjem, M. I.; Fanning, E. (2004). "The replicon revisited: An old model learns new tricks in metazoan chromosomes". EMBO Reports 5 (7): 686–691. doi:10.1038/sj.embor.7400185. PMID 15229645. PMC 1299096. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1299096/. 
  27. ↑ 27.0 27.1 Remus, D.; Beall, E. L.; Botchan, M. R. (2004). "DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding". The EMBO Journal 23 (4): 897–907. doi:10.1038/sj.emboj.7600077. PMID 14765124. PMC 380993. //www.ncbi.nlm.nih.gov/pmc/articles/PMC380993/. 
  28. ↑ Vashee, S.; Cvetic, C.; Lu, W.; Simancek, P.; Kelly, T. J.; Walter, J. C. (2003). "Sequence-independent DNA binding and replication initiation by the human origin recognition complex". Genes & Development 17 (15): 1894–2708. doi:10.1101/gad.1084203. PMID 12897055. PMC 196240. //www.ncbi.nlm.nih.gov/pmc/articles/PMC196240/. 
  29. ↑ 29.0 29.1 Shen, Z.; Sathyan, K. M.; Geng, Y.; Zheng, R.; Chakraborty, A.; Freeman, B.; Wang, F.; Prasanth, K. V. et al. (2010). "A WD-repeat protein stabilizes ORC binding to chromatin". Molecular Cell 40 (1): 99–111. doi:10.1016/j.molcel.2010.09.021. PMID 20932478. PMC 5201136. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5201136/. 
  30. ↑ 30.0 30.1 Dorn, E. S.; Cook, J. G. (2011). "Nucleosomes in the neighborhood: New roles for chromatin modifications in replication origin control". Epigenetics 6 (5): 552–559. doi:10.4161/epi.6.5.15082. PMID 21364325. PMC 3230546. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3230546/. 
  31. ↑ 31.0 31.1 31.2 Aladjem, M. I.; Redon, C. E. (2017). "Order from clutter: Selective interactions at mammalian replication origins". Nature Reviews. Genetics 18 (2): 101–116. doi:10.1038/nrg.2016.141. PMID 27867195. PMC 6596300. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6596300/. 
  32. ↑ 32.0 32.1 Fragkos, M.; Ganier, O.; Coulombe, P.; Méchali, M. (2015). "DNA replication origin activation in space and time". Nature Reviews. Molecular Cell Biology 16 (6): 360–374. doi:10.1038/nrm4002. PMID 25999062. 
  33. ↑ 33.0 33.1 33.2 Prioleau, M. N.; MacAlpine, D. M. (2016). "DNA replication origins-where do we begin?". Genes & Development 30 (15): 1683–1697. doi:10.1101/gad.285114.116. PMID 27542827. PMC 5002974. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5002974/. 
  34. ↑ Cayrou, C.; Coulombe, P.; Puy, A.; Rialle, S.; Kaplan, N.; Segal, E.; Méchali, M. (2012). "New insights into replication origin characteristics in metazoans". Cell Cycle (Georgetown, Tex.) 11 (4): 658–667. doi:10.4161/cc.11.4.19097. PMID 22373526. PMC 3318102. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3318102/. 
  35. ↑ Lombraña, R.; Almeida, R.; Álvarez, A.; Gómez, M. (2015). "R-loops and initiation of DNA replication in human cells: A missing link?". Frontiers in Genetics 6: 158. doi:10.3389/fgene.2015.00158. PMID 25972891. PMC 4412123. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4412123/. 
  36. ↑ Jang, S. M.; Zhang, Y.; Utani, K.; Fu, H.; Redon, C. E.; Marks, A. B.; Smith, O. K.; Redmond, C. J. et al. (2018). "The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin". Nature Communications 9 (1): 2782. doi:10.1038/s41467-018-05177-6. PMID 30018425. PMC 6050238. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6050238/. 
  37. ↑ Zakian, V. A.; Scott, J. F. (1982). "Construction, replication, and chromatin structure of TRP1 RI circle, a multiple-copy synthetic plasmid derived from Saccharomyces cerevisiae chromosomal DNA". Molecular and Cellular Biology 2 (3): 221–232. doi:10.1128/mcb.2.3.221-232.1982. PMID 6287231. PMC 369780. //www.ncbi.nlm.nih.gov/pmc/articles/PMC369780/. 
  38. ↑ Rhodes, N.; Company, M.; Errede, B. (1990). "A yeast-Escherichia coli shuttle vector containing the M13 origin of replication". Plasmid 23 (2): 159–162. doi:10.1016/0147-619x(90)90036-c. PMID 2194231. 
  39. ↑ Paululat, A.; Heinisch, J. J. (2012). "New yeast/E. Coli/Drosophila triple shuttle vectors for efficient generation of Drosophila P element transformation constructs". Gene 511 (2): 300–305. doi:10.1016/j.gene.2012.09.058. PMID 23026211. 
  40. ↑ Ryan, V. T.; Grimwade, J. E.; Camara, J. E.; Crooke, E.; Leonard, A. C. (2004). "Escherichia coli prereplication complex assembly is regulated by dynamic interplay among Fis, IHF and DnaA". Molecular Microbiology 51 (5): 1347–1359. doi:10.1046/j.1365-2958.2003.03906.x. PMID 14982629. 
  41. ↑ 41.0 41.1 MacKiewicz, P.; Zakrzewska-Czerwinska, J.; Zawilak, A.; Dudek, M. R.; Cebrat, S. (2004). "Where does bacterial replication start? Rules for predicting the oriC region". Nucleic Acids Research 32 (13): 3781–3791. doi:10.1093/nar/gkh699. PMID 15258248. PMC 506792. //www.ncbi.nlm.nih.gov/pmc/articles/PMC506792/. 
  42. ↑ 42.0 42.1 42.2 Luo, H.; Gao, F. (2019). "DoriC 10.0: An updated database of replication origins in prokaryotic genomes including chromosomes and plasmids". Nucleic Acids Research 47 (D1): D74–D77. doi:10.1093/nar/gky1014. PMID 30364951. PMC 6323995. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6323995/. 
  43. ↑ 43.0 43.1 Fuller, R. S.; Funnell, B. E.; Kornberg, A. (1984). "The dnaA protein complex with the e. Coli chromosomal replication origin (OriC) and other DNA sites". Cell 38 (3): 889–900. doi:10.1016/0092-8674(84)90284-8. PMID 6091903. 
  44. ↑ Fuller, R. S.; Kornberg, A. (1983). "Purified dnaA protein in initiation of replication at the Escherichia coli chromosomal origin of replication". Proceedings of the National Academy of Sciences of the United States of America 80 (19): 5817–5821. doi:10.1073/pnas.80.19.5817. PMID 6310593. PMC 390166. //www.ncbi.nlm.nih.gov/pmc/articles/PMC390166/. 
  45. ↑ Jakimowicz, D.; Majka, J.; Messer, W.; Speck, C.; Fernandez, M.; Cruz Martin, M.; Sanchez, J.; Schauwecker, F. et al. (1998). "Structural elements of the Streptomyces oriC region and their interactions with the DnaA protein". Microbiology (Reading, England) 144 ( Pt 5) (5): 1281–1290. doi:10.1099/00221287-144-5-1281. PMID 9611803. 
  46. ↑ Tsodikov, O. V.; Biswas, T. (2011). "Structural and thermodynamic signatures of DNA recognition by Mycobacterium tuberculosis DnaA". Journal of Molecular Biology 410 (3): 461–476. doi:10.1016/j.jmb.2011.05.007. PMID 21620858. 
  47. ↑ Costa, A.; Hood, I. V.; Berger, J. M. (2013). "Mechanisms for initiating cellular DNA replication". Annual Review of Biochemistry 82: 25–54. doi:10.1146/annurev-biochem-052610-094414. PMID 23746253. PMC 4696014. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4696014/. 
  48. ↑ Wolański, M.; Donczew, R.; Zawilak-Pawlik, A.; Zakrzewska-Czerwińska, J. (2014). "OriC-encoded instructions for the initiation of bacterial chromosome replication". Frontiers in Microbiology 5: 735. doi:10.3389/fmicb.2014.00735. PMID 25610430. PMC 4285127. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4285127/. 
  49. ↑ 49.0 49.1 Messer, W.; Blaesing, F.; Majka, J.; Nardmann, J.; Schaper, S.; Schmidt, A.; Seitz, H.; Speck, C. et al. (1999). "Functional domains of DnaA proteins". Biochimie 81 (8–9): 819–825. doi:10.1016/s0300-9084(99)00215-1. PMID 10572294. 
  50. ↑ Sutton, M. D.; Kaguni, J. M. (1997). "The Escherichia coli dnaA gene: Four functional domains". Journal of Molecular Biology 274 (4): 546–561. doi:10.1006/jmbi.1997.1425. PMID 9417934. 
  51. ↑ Speck, C.; Messer, W. (2001). "Mechanism of origin unwinding: Sequential binding of DnaA to double- and single-stranded DNA". The EMBO Journal 20 (6): 1469–1476. doi:10.1093/emboj/20.6.1469. PMID 11250912. PMC 145534. //www.ncbi.nlm.nih.gov/pmc/articles/PMC145534/. 
  52. ↑ 52.0 52.1 Fujikawa, N.; Kurumizaka, H.; Nureki, O.; Terada, T.; Shirouzu, M.; Katayama, T.; Yokoyama, S. (2003). "Structural basis of replication origin recognition by the DnaA protein". Nucleic Acids Research 31 (8): 2077–2086. doi:10.1093/nar/gkg309. PMID 12682358. PMC 153737. //www.ncbi.nlm.nih.gov/pmc/articles/PMC153737/. 
  53. ↑ 53.0 53.1 53.2 Duderstadt, K. E.; Chuang, K.; Berger, J. M. (2011). "DNA stretching by bacterial initiators promotes replication origin opening". Nature 478 (7368): 209–213. doi:10.1038/nature10455. PMID 21964332. PMC 3192921. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3192921/. 
  54. ↑ 54.0 54.1 Erzberger, J. P.; Pirruccello, M. M.; Berger, J. M. (2002). "The structure of bacterial DnaA: Implications for general mechanisms underlying DNA replication initiation". The EMBO Journal 21 (18): 4763–4773. doi:10.1093/emboj/cdf496. PMID 12234917. PMC 126292. //www.ncbi.nlm.nih.gov/pmc/articles/PMC126292/. 
  55. ↑ Iyer, L. M.; Leipe, D. D.; Koonin, E. V.; Aravind, L. (2004). "Evolutionary history and higher order classification of AAA+ ATPases". Journal of Structural Biology 146 (1–2): 11–31. doi:10.1016/j.jsb.2003.10.010. PMID 15037234. 
  56. ↑ Sutton, M. D.; Kaguni, J. M. (1997). "Threonine 435 of Escherichia coli DnaA protein confers sequence-specific DNA binding activity". The Journal of Biological Chemistry 272 (37): 23017–23024. doi:10.1074/jbc.272.37.23017. PMID 9287298. 
  57. ↑ Bramhill, D.; Kornberg, A. (1988). "A model for initiation at origins of DNA replication". Cell 54 (7): 915–918. doi:10.1016/0092-8674(88)90102-x. PMID 2843291. 
  58. ↑ Rozgaja, T. A.; Grimwade, J. E.; Iqbal, M.; Czerwonka, C.; Vora, M.; Leonard, A. C. (2011). "Two oppositely oriented arrays of low-affinity recognition sites in oriC guide progressive binding of DnaA during Escherichia coli pre-RC assembly". Molecular Microbiology 82 (2): 475–488. doi:10.1111/j.1365-2958.2011.07827.x. PMID 21895796. PMC 3192301. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3192301/. 
  59. ↑ Zawilak-Pawlik, A.; Kois, A.; Majka, J.; Jakimowicz, D.; Smulczyk-Krawczyszyn, A.; Messer, W.; Zakrzewska-Czerwińska, J. (2005). "Architecture of bacterial replication initiation complexes: Orisomes from four unrelated bacteria". The Biochemical Journal 389 (Pt 2): 471–481. doi:10.1042/BJ20050143. PMID 15790315. PMC 1175125. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1175125/. 
  60. ↑ 60.0 60.1 Grimwade, J. E.; Rozgaja, T. A.; Gupta, R.; Dyson, K.; Rao, P.; Leonard, A. C. (2018). "Origin recognition is the predominant role for DnaA-ATP in initiation of chromosome replication". Nucleic Acids Research 46 (12): 6140–6151. doi:10.1093/nar/gky457. PMID 29800247. PMC 6158602. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6158602/. 
  61. ↑ Sakiyama, Y.; Kasho, K.; Noguchi, Y.; Kawakami, H.; Katayama, T. (2017). "Regulatory dynamics in the ternary DnaA complex for initiation of chromosomal replication in Escherichia coli". Nucleic Acids Research 45 (21): 12354–12373. doi:10.1093/nar/gkx914. PMID 29040689. PMC 5716108. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5716108/. 
  62. ↑ Matsui, M.; Oka, A.; Takanami, M.; Yasuda, S.; Hirota, Y. (1985). "Sites of dnaA protein-binding in the replication origin of the Escherichia coli K-12 chromosome". Journal of Molecular Biology 184 (3): 529–533. doi:10.1016/0022-2836(85)90299-2. PMID 2995681. 
  63. ↑ Margulies, C.; Kaguni, J. M. (1996). "Ordered and sequential binding of DnaA protein to oriC, the chromosomal origin of Escherichia coli". The Journal of Biological Chemistry 271 (29): 17035–17040. doi:10.1074/jbc.271.29.17035. PMID 8663334. 
  64. ↑ Schaper, S.; Messer, W. (1995). "Interaction of the initiator protein DnaA of Escherichia coli with its DNA target". The Journal of Biological Chemistry 270 (29): 17622–17626. doi:10.1074/jbc.270.29.17622. PMID 7615570. 
  65. ↑ Weigel, C.; Schmidt, A.; Rückert, B.; Lurz, R.; Messer, W. (1997). "DnaA protein binding to individual DnaA boxes in the Escherichia coli replication origin, oriC". The EMBO Journal 16 (21): 6574–6583. doi:10.1093/emboj/16.21.6574. PMID 9351837. PMC 1170261. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1170261/. 
  66. ↑ Samitt, C. E.; Hansen, F. G.; Miller, J. F.; Schaechter, M. (1989). "In vivo studies of DnaA binding to the origin of replication of Escherichia coli". The EMBO Journal 8 (3): 989–993. doi:10.1002/j.1460-2075.1989.tb03462.x. PMID 2542031. PMC 400901. //www.ncbi.nlm.nih.gov/pmc/articles/PMC400901/. 
  67. ↑ McGarry, K. C.; Ryan, V. T.; Grimwade, J. E.; Leonard, A. C. (2004). "Two discriminatory binding sites in the Escherichia coli replication origin are required for DNA strand opening by initiator DnaA-ATP". Proceedings of the National Academy of Sciences of the United States of America 101 (9): 2811–2816. doi:10.1073/pnas.0400340101. PMID 14978287. PMC 365702. //www.ncbi.nlm.nih.gov/pmc/articles/PMC365702/. 
  68. ↑ Kawakami, H.; Keyamura, K.; Katayama, T. (2005). "Formation of an ATP-DnaA-specific initiation complex requires DnaA Arginine 285, a conserved motif in the AAA+ protein family". The Journal of Biological Chemistry 280 (29): 27420–27430. doi:10.1074/jbc.M502764200. PMID 15901724. 
  69. ↑ Speck, C.; Weigel, C.; Messer, W. (1999). "ATP- and ADP-dnaA protein, a molecular switch in gene regulation". The EMBO Journal 18 (21): 6169–6176. doi:10.1093/emboj/18.21.6169. PMID 10545126. PMC 1171680. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1171680/. 
  70. ↑ Miller, D. T.; Grimwade, J. E.; Betteridge, T.; Rozgaja, T.; Torgue, J. J.; Leonard, A. C. (2009). "Bacterial origin recognition complexes direct assembly of higher-order DnaA oligomeric structures". Proceedings of the National Academy of Sciences of the United States of America 106 (44): 18479–18484. doi:10.1073/pnas.0909472106. PMID 19833870. PMC 2773971. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2773971/. 
  71. ↑ 71.0 71.1 71.2 Erzberger, J. P.; Mott, M. L.; Berger, J. M. (2006). "Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling". Nature Structural & Molecular Biology 13 (8): 676–683. doi:10.1038/nsmb1115. PMID 16829961. 
  72. ↑ Zorman, S.; Seitz, H.; Sclavi, B.; Strick, T. R. (2012). "Topological characterization of the DnaA-oriC complex using single-molecule nanomanipuation". Nucleic Acids Research 40 (15): 7375–7383. doi:10.1093/nar/gks371. PMID 22581769. PMC 3424547. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3424547/. 
  73. ↑ 73.0 73.1 Richardson, T. T.; Harran, O.; Murray, H. (2016). "The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding". Nature 534 (7607): 412–416. doi:10.1038/nature17962. PMID 27281207. PMC 4913881. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4913881/. 
  74. ↑ Duderstadt, K. E.; Mott, M. L.; Crisona, N. J.; Chuang, K.; Yang, H.; Berger, J. M. (2010). "Origin remodeling and opening in bacteria rely on distinct assembly states of the DnaA initiator". The Journal of Biological Chemistry 285 (36): 28229–28239. doi:10.1074/jbc.M110.147975. PMID 20595381. PMC 2934688. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2934688/. 
  75. ↑ Ozaki, S.; Katayama, T. (2012). "Highly organized DnaA-oriC complexes recruit the single-stranded DNA for replication initiation". Nucleic Acids Research 40 (4): 1648–1665. doi:10.1093/nar/gkr832. PMID 22053082. PMC 3287180. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3287180/. 
  76. ↑ Myllykallio, H.; Lopez, P.; López-García, P.; Heilig, R.; Saurin, W.; Zivanovic, Y.; Philippe, H.; Forterre, P. (2000). "Bacterial mode of replication with eukaryotic-like machinery in a hyperthermophilic archaeon". Science 288 (5474): 2212–2215. doi:10.1126/science.288.5474.2212. PMID 10864870. 
  77. ↑ 77.0 77.1 77.2 Norais, C.; Hawkins, M.; Hartman, A. L.; Eisen, J. A.; Myllykallio, H.; Allers, T. (2007). "Genetic and physical mapping of DNA replication origins in Haloferax volcanii". PLOS Genetics 3 (5): e77. doi:10.1371/journal.pgen.0030077. PMID 17511521. PMC 1868953. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1868953/. 
  78. ↑ 78.0 78.1 Hawkins, M.; Malla, S.; Blythe, M. J.; Nieduszynski, C. A.; Allers, T. (2013). "Accelerated growth in the absence of DNA replication origins". Nature 503 (7477): 544–547. doi:10.1038/nature12650. PMID 24185008. PMC 3843117. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3843117/. 
  79. ↑ Wu, Z.; Liu, J.; Yang, H.; Liu, H.; Xiang, H. (2014). "Multiple replication origins with diverse control mechanisms in Haloarcula hispanica". Nucleic Acids Research 42 (4): 2282–2294. doi:10.1093/nar/gkt1214. PMID 24271389. PMC 3936714. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3936714/. 
  80. ↑ Pelve, E. A.; Martens-Habbena, W.; Stahl, D. A.; Bernander, R. (2013). "Mapping of active replication origins in vivo in thaum- and euryarchaeal replicons". Molecular Microbiology 90 (3): 538–550. doi:10.1111/mmi.12382. PMID 23991938. 
  81. ↑ Pelve, E. A.; Lindås, A. C.; Knöppel, A.; Mira, A.; Bernander, R. (2012). "Four chromosome replication origins in the archaeon Pyrobaculum calidifontis". Molecular Microbiology 85 (5): 986–995. doi:10.1111/j.1365-2958.2012.08155.x. PMID 22812406. 
  82. ↑ 82.00 82.01 82.02 82.03 82.04 82.05 82.06 82.07 82.08 82.09 Robinson, N. P.; Dionne, I.; Lundgren, M.; Marsh, V. L.; Bernander, R.; Bell, S. D. (2004). "Identification of two origins of replication in the single chromosome of the archaeon Sulfolobus solfataricus". Cell 116 (1): 25–38. doi:10.1016/s0092-8674(03)01034-1. PMID 14718164. 
  83. ↑ 83.0 83.1 Lundgren, M.; Andersson, A.; Chen, L.; Nilsson, P.; Bernander, R. (2004). "Three replication origins in Sulfolobus species: Synchronous initiation of chromosome replication and asynchronous termination". Proceedings of the National Academy of Sciences of the United States of America 101 (18): 7046–7051. doi:10.1073/pnas.0400656101. PMID 15107501. PMC 406463. //www.ncbi.nlm.nih.gov/pmc/articles/PMC406463/. 
  84. ↑ Bell, S. D. (2017). "Initiation of DNA Replication in the Archaea". Advances in Experimental Medicine and Biology 1042: 99–115. doi:10.1007/978-981-10-6955-0_5. ISBN 978-981-10-6954-3. PMID 29357055. 
  85. ↑ Ausiannikava, D.; Allers, T. (2017). "Diversity of DNA Replication in the Archaea". Genes 8 (2): 56. doi:10.3390/genes8020056. PMID 28146124. PMC 5333045. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5333045/. 
  86. ↑ Wu, Z.; Liu, J.; Yang, H.; Xiang, H. (2014). "DNA replication origins in archaea". Frontiers in Microbiology 5: 179. doi:10.3389/fmicb.2014.00179. PMID 24808892. PMC 4010727. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4010727/. 
  87. ↑ Matsunaga, F.; Forterre, P.; Ishino, Y.; Myllykallio, H. (2001). "In vivo interactions of archaeal Cdc6/Orc1 and minichromosome maintenance proteins with the replication origin". Proceedings of the National Academy of Sciences of the United States of America 98 (20): 11152–11157. doi:10.1073/pnas.191387498. PMID 11562464. PMC 58699. //www.ncbi.nlm.nih.gov/pmc/articles/PMC58699/. 
  88. ↑ Wu, Z.; Liu, H.; Liu, J.; Liu, X.; Xiang, H. (2012). "Diversity and evolution of multiple orc/Cdc6-adjacent replication origins in haloarchaea". BMC Genomics 13: 478. doi:10.1186/1471-2164-13-478. PMID 22978470. PMC 3528665. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3528665/. 
  89. ↑ Bell, S. D. (2012). "Archaeal orc1/Cdc6 proteins". Sub-Cellular Biochemistry 62: 59–69. doi:10.1007/978-94-007-4572-8_4. ISBN 978-94-007-4571-1. PMID 22918580. 
  90. ↑ 90.0 90.1 90.2 90.3 90.4 Samson, R. Y.; Xu, Y.; Gadelha, C.; Stone, T. A.; Faqiri, J. N.; Li, D.; Qin, N.; Pu, F. et al. (2013). "Specificity and function of archaeal DNA replication initiator proteins". Cell Reports 3 (2): 485–496. doi:10.1016/j.celrep.2013.01.002. PMID 23375370. PMC 3607249. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3607249/. 
  91. ↑ 91.0 91.1 91.2 91.3 Grainge, I.; Gaudier, M.; Schuwirth, B. S.; Westcott, S. L.; Sandall, J.; Atanassova, N.; Wigley, D. B. (2006). "Biochemical analysis of a DNA replication origin in the archaeon Aeropyrum pernix". Journal of Molecular Biology 363 (2): 355–369. doi:10.1016/j.jmb.2006.07.076. PMID 16978641. 
  92. ↑ 92.0 92.1 Robinson, N. P.; Bell, S. D. (2007). "Extrachromosomal element capture and the evolution of multiple replication origins in archaeal chromosomes". Proceedings of the National Academy of Sciences of the United States of America 104 (14): 5806–5811. doi:10.1073/pnas.0700206104. PMID 17392430. PMC 1851573. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1851573/. 
  93. ↑ 93.0 93.1 93.2 Robinson, N. P.; Blood, K. A.; McCallum, S. A.; Edwards, P. A.; Bell, S. D. (2007). "Sister chromatid junctions in the hyperthermophilic archaeon Sulfolobus solfataricus". The EMBO Journal 26 (3): 816–824. doi:10.1038/sj.emboj.7601529. PMID 17255945. PMC 1794387. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1794387/. 
  94. ↑ 94.0 94.1 94.2 94.3 94.4 94.5 94.6 94.7 Dueber, E. L.; Corn, J. E.; Bell, S. D.; Berger, J. M. (2007). "Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex". Science 317 (5842): 1210–1213. doi:10.1126/science.1143690. PMID 17761879. 
  95. ↑ 95.0 95.1 95.2 95.3 95.4 95.5 95.6 Gaudier, M.; Schuwirth, B. S.; Westcott, S. L.; Wigley, D. B. (2007). "Structural basis of DNA replication origin recognition by an ORC protein". Science 317 (5842): 1213–1216. doi:10.1126/science.1143664. PMID 17761880. 
  96. ↑ Capaldi, S. A.; Berger, J. M. (2004). "Biochemical characterization of Cdc6/Orc1 binding to the replication origin of the euryarchaeon Methanothermobacter thermoautotrophicus". Nucleic Acids Research 32 (16): 4821–4832. doi:10.1093/nar/gkh819. PMID 15358831. PMC 519113. //www.ncbi.nlm.nih.gov/pmc/articles/PMC519113/. 
  97. ↑ Liu, J.; Smith, C. L.; Deryckere, D.; Deangelis, K.; Martin, G. S.; Berger, J. M. (2000). "Structure and function of Cdc6/Cdc18: Implications for origin recognition and checkpoint control". Molecular Cell 6 (3): 637–648. doi:10.1016/s1097-2765(00)00062-9. PMID 11030343. 
  98. ↑ Singleton, M. R.; Morales, R.; Grainge, I.; Cook, N.; Isupov, M. N.; Wigley, D. B. (2004). "Conformational changes induced by nucleotide binding in Cdc6/ORC from Aeropyrum pernix". Journal of Molecular Biology 343 (3): 547–557. doi:10.1016/j.jmb.2004.08.044. PMID 15465044. 
  99. ↑ Matsunaga, F.; Norais, C.; Forterre, P.; Myllykallio, H. (2003). "Identification of short 'eukaryotic' Okazaki fragments synthesized from a prokaryotic replication origin". EMBO Reports 4 (2): 154–158. doi:10.1038/sj.embor.embor732. PMID 12612604. PMC 1315830. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1315830/. 
  100. ↑ Berquist, B. R.; Dassarma, S. (2003). "An archaeal chromosomal autonomously replicating sequence element from an extreme halophile, Halobacterium sp. Strain NRC-1". Journal of Bacteriology 185 (20): 5959–5966. doi:10.1128/JB.185.20.5959-5966.2003. PMID 14526006. PMC 225043. //www.ncbi.nlm.nih.gov/pmc/articles/PMC225043/. 
  101. ↑ Kasiviswanathan, R.; Shin, J. H.; Kelman, Z. (2005). "Interactions between the archaeal Cdc6 and MCM proteins modulate their biochemical properties". Nucleic Acids Research 33 (15): 4940–4950. doi:10.1093/nar/gki807. PMID 16150924. PMC 1201339. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1201339/. 
  102. ↑ Samson, R. Y.; Abeyrathne, P. D.; Bell, S. D. (2016). "Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins". Molecular Cell 61 (2): 287–296. doi:10.1016/j.molcel.2015.12.005. PMID 26725007. PMC 4724246. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4724246/. 
  103. ↑ Dueber, E. C.; Costa, A.; Corn, J. E.; Bell, S. D.; Berger, J. M. (2011). "Molecular determinants of origin discrimination by Orc1 initiators in archaea". Nucleic Acids Research 39 (9): 3621–3631. doi:10.1093/nar/gkq1308. PMID 21227921. PMC 3089459. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3089459/. 
  104. ↑ Matsunaga, F.; Takemura, K.; Akita, M.; Adachi, A.; Yamagami, T.; Ishino, Y. (2010). "Localized melting of duplex DNA by Cdc6/Orc1 at the DNA replication origin in the hyperthermophilic archaeon Pyrococcus furiosus". Extremophiles : Life Under Extreme Conditions 14 (1): 21–31. doi:10.1007/s00792-009-0284-9. PMID 19787415. 
  105. ↑ Onishi, M.; Liou, G. G.; Buchberger, J. R.; Walz, T.; Moazed, D. (2007). "Role of the conserved Sir3-BAH domain in nucleosome binding and silent chromatin assembly". Molecular Cell 28 (6): 1015–1028. doi:10.1016/j.molcel.2007.12.004. PMID 18158899. 
  106. ↑ 106.0 106.1 Kuo, A. J.; Song, J.; Cheung, P.; Ishibe-Murakami, S.; Yamazoe, S.; Chen, J. K.; Patel, D. J.; Gozani, O. (2012). "The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome". Nature 484 (7392): 115–119. doi:10.1038/nature10956. PMID 22398447. PMC 3321094. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3321094/. 
  107. ↑ 107.0 107.1 Bleichert, F.; Botchan, M. R.; Berger, J. M. (2017). "Mechanisms for initiating cellular DNA replication". Science 355 (6327). doi:10.1126/science.aah6317. PMID 28209641. 
  108. ↑ 108.0 108.1 Gambus, A.; Khoudoli, G. A.; Jones, R. C.; Blow, J. J. (2011). "MCM2-7 form double hexamers at licensed origins in Xenopus egg extract". The Journal of Biological Chemistry 286 (13): 11855–11864. doi:10.1074/jbc.M110.199521. PMID 21282109. PMC 3064236. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3064236/. 
  109. ↑ 109.0 109.1 Remus, D.; Beuron, F.; Tolun, G.; Griffith, J. D.; Morris, E. P.; Diffley, J. F. (2009). "Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing". Cell 139 (4): 719–730. doi:10.1016/j.cell.2009.10.015. PMID 19896182. PMC 2804858. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2804858/. 
  110. ↑ 110.0 110.1 Evrin, C.; Clarke, P.; Zech, J.; Lurz, R.; Sun, J.; Uhle, S.; Li, H.; Stillman, B. et al. (2009). "A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication". Proceedings of the National Academy of Sciences of the United States of America 106 (48): 20240–20245. doi:10.1073/pnas.0911500106. PMID 19910535. PMC 2787165. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2787165/. 
  111. ↑ Ge, X. Q.; Jackson, D. A.; Blow, J. J. (2007). "Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress". Genes & Development 21 (24): 3331–3341. doi:10.1101/gad.457807. PMID 18079179. PMC 2113033. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2113033/. 
  112. ↑ Ibarra, A.; Schwob, E.; Méndez, J. (2008). "Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication". Proceedings of the National Academy of Sciences of the United States of America 105 (26): 8956–8961. doi:10.1073/pnas.0803978105. PMID 18579778. PMC 2449346. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2449346/. 
  113. ↑ Stinchcomb, D. T.; Struhl, K.; Davis, R. W. (1979). "Isolation and characterisation of a yeast chromosomal replicator". Nature 282 (5734): 39–43. doi:10.1038/282039a0. PMID 388229. 
  114. ↑ Huberman, J. A.; Spotila, L. D.; Nawotka, K. A.; El-Assouli, S. M.; Davis, L. R. (1987). "The in vivo replication origin of the yeast 2 microns plasmid". Cell 51 (3): 473–481. doi:10.1016/0092-8674(87)90643-x. PMID 3311385. 
  115. ↑ Brewer, B. J.; Fangman, W. L. (1987). "The localization of replication origins on ARS plasmids in S. Cerevisiae.". Cell 51 (3): 463–471. doi:10.1016/0092-8674(87)90642-8. PMID 2822257. 
  116. ↑ 116.0 116.1 Marahrens, Y.; Stillman, B. (1992). "A yeast chromosomal origin of DNA replication defined by multiple functional elements". Science 255 (5046): 817–823. doi:10.1126/science.1536007. PMID 1536007. 
  117. ↑ Rao, H.; Marahrens, Y.; Stillman, B. (1994). "Functional conservation of multiple elements in yeast chromosomal replicators". Molecular and Cellular Biology 14 (11): 7643–7651. doi:10.1128/mcb.14.11.7643-7651.1994. PMID 7935478. PMC 359300. //www.ncbi.nlm.nih.gov/pmc/articles/PMC359300/. 
  118. ↑ Broach, J. R.; Li, Y. Y.; Feldman, J.; Jayaram, M.; Abraham, J.; Nasmyth, K. A.; Hicks, J. B. (1983). "Localization and sequence analysis of yeast origins of DNA replication". Cold Spring Harbor Symposia on Quantitative Biology 47 Pt 2: 1165–1173. doi:10.1101/sqb.1983.047.01.132. PMID 6345070. 
  119. ↑ Celniker, S. E.; Sweder, K.; Srienc, F.; Bailey, J. E.; Campbell, J. L. (1984). "Deletion mutations affecting autonomously replicating sequence ARS1 of Saccharomyces cerevisiae". Molecular and Cellular Biology 4 (11): 2455–2466. doi:10.1128/mcb.4.11.2455-2466.1984. PMID 6392851. PMC 369077. //www.ncbi.nlm.nih.gov/pmc/articles/PMC369077/. 
  120. ↑ Rao, H.; Stillman, B. (1995). "The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators". Proceedings of the National Academy of Sciences of the United States of America 92 (6): 2224–2228. doi:10.1073/pnas.92.6.2224. PMID 7892251. PMC 42456. //www.ncbi.nlm.nih.gov/pmc/articles/PMC42456/. 
  121. ↑ Rowley, A.; Cocker, J. H.; Harwood, J.; Diffley, J. F. (1995). "Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC". The EMBO Journal 14 (11): 2631–2641. doi:10.1002/j.1460-2075.1995.tb07261.x. PMID 7781615. PMC 398377. //www.ncbi.nlm.nih.gov/pmc/articles/PMC398377/. 
  122. ↑ Bell, S. P.; Stillman, B. (1992). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature 357 (6374): 128–134. doi:10.1038/357128a0. PMID 1579162. 
  123. ↑ 123.0 123.1 123.2 123.3 Li, N.; Lam, W. H.; Zhai, Y.; Cheng, J.; Cheng, E.; Zhao, Y.; Gao, N.; Tye, B. K. (2018). "Structure of the origin recognition complex bound to DNA replication origin". Nature 559 (7713): 217–222. doi:10.1038/s41586-018-0293-x. PMID 29973722. 
  124. ↑ Bleichert, F.; Botchan, M. R.; Berger, J. M. (2015). "Crystal structure of the eukaryotic origin recognition complex". Nature 519 (7543): 321–326. doi:10.1038/nature14239. PMID 25762138. PMC 4368505. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4368505/. 
  125. ↑ Sun, J.; Evrin, C.; Samel, S. A.; Fernández-Cid, A.; Riera, A.; Kawakami, H.; Stillman, B.; Speck, C. et al. (2013). "Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA". Nature Structural & Molecular Biology 20 (8): 944–951. doi:10.1038/nsmb.2629. PMID 23851460. PMC 3735830. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3735830/. 
  126. ↑ Kawakami, H.; Ohashi, E.; Kanamoto, S.; Tsurimoto, T.; Katayama, T. (2015). "Specific binding of eukaryotic ORC to DNA replication origins depends on highly conserved basic residues". Scientific Reports 5: 14929. doi:10.1038/srep14929. PMID 26456755. PMC 4601075. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4601075/. 
  127. ↑ Palzkill, T. G.; Newlon, C. S. (1988). "A yeast replication origin consists of multiple copies of a small conserved sequence". Cell 53 (3): 441–450. doi:10.1016/0092-8674(88)90164-x. PMID 3284655. 
  128. ↑ Wilmes, G. M.; Bell, S. P. (2002). "The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation". Proceedings of the National Academy of Sciences of the United States of America 99 (1): 101–106. doi:10.1073/pnas.012578499. PMID 11756674. PMC 117521. //www.ncbi.nlm.nih.gov/pmc/articles/PMC117521/. 
  129. ↑ Coster, G.; Diffley JFX (2017). "Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading". Science 357 (6348): 314–318. doi:10.1126/science.aan0063. PMID 28729513. PMC 5608077. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5608077/. 
  130. ↑ Zou, L.; Stillman, B. (2000). "Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase". Molecular and Cellular Biology 20 (9): 3086–3096. doi:10.1128/MCB.20.9.3086-3096.2000. PMID 10757793. PMC 85601. //www.ncbi.nlm.nih.gov/pmc/articles/PMC85601/. 
  131. ↑ Lipford, J. R.; Bell, S. P. (2001). "Nucleosomes positioned by ORC facilitate the initiation of DNA replication". Molecular Cell 7 (1): 21–30. doi:10.1016/s1097-2765(01)00151-4. PMID 11172708. 
  132. ↑ Diffley, J. F.; Cocker, J. H. (1992). "Protein-DNA interactions at a yeast replication origin". Nature 357 (6374): 169–172. doi:10.1038/357169a0. PMID 1579168. 
  133. ↑ Diffley, J. F.; Stillman, B. (1988). "Purification of a yeast protein that binds to origins of DNA replication and a transcriptional silencer". Proceedings of the National Academy of Sciences of the United States of America 85 (7): 2120–2124. doi:10.1073/pnas.85.7.2120. PMID 3281162. PMC 279940. //www.ncbi.nlm.nih.gov/pmc/articles/PMC279940/. 
  134. ↑ Miotto, B.; Ji, Z.; Struhl, K. (2016). "Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers". Proceedings of the National Academy of Sciences of the United States of America 113 (33): E4810-9. doi:10.1073/pnas.1609060113. PMID 27436900. PMC 4995967. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4995967/. 
  135. ↑ 135.0 135.1 MacAlpine, H. K.; Gordân, R.; Powell, S. K.; Hartemink, A. J.; MacAlpine, D. M. (2010). "Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading". Genome Research 20 (2): 201–211. doi:10.1101/gr.097873.109. PMID 19996087. PMC 2813476. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2813476/. 
  136. ↑ 136.0 136.1 Eaton, M. L.; Prinz, J. A.; MacAlpine, H. K.; Tretyakov, G.; Kharchenko, P. V.; MacAlpine, D. M. (2011). "Chromatin signatures of the Drosophila replication program". Genome Research 21 (2): 164–174. doi:10.1101/gr.116038.110. PMID 21177973. PMC 3032920. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3032920/. 
  137. ↑ 137.0 137.1 Dellino, G. I.; Cittaro, D.; Piccioni, R.; Luzi, L.; Banfi, S.; Segalla, S.; Cesaroni, M.; Mendoza-Maldonado, R. et al. (2013). "Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing". Genome Research 23 (1): 1–11. doi:10.1101/gr.142331.112. PMID 23187890. PMC 3530669. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3530669/. 
  138. ↑ Cayrou, C.; Ballester, B.; Peiffer, I.; Fenouil, R.; Coulombe, P.; Andrau, J. C.; Van Helden, J.; Méchali, M. (2015). "The chromatin environment shapes DNA replication origin organization and defines origin classes". Genome Research 25 (12): 1873–1885. doi:10.1101/gr.192799.115. PMID 26560631. PMC 4665008. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4665008/. 
  139. ↑ 139.0 139.1 139.2 139.3 Cayrou, C.; Coulombe, P.; Vigneron, A.; Stanojcic, S.; Ganier, O.; Peiffer, I.; Rivals, E.; Puy, A. et al. (2011). "Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features". Genome Research 21 (9): 1438–1449. doi:10.1101/gr.121830.111. PMID 21750104. PMC 3166829. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3166829/. 
  140. ↑ 140.0 140.1 Lubelsky, Y.; Sasaki, T.; Kuipers, M. A.; Lucas, I.; Le Beau, M. M.; Carignon, S.; Debatisse, M.; Prinz, J. A. et al. (2011). "Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone". Nucleic Acids Research 39 (8): 3141–3155. doi:10.1093/nar/gkq1276. PMID 21148149. PMC 3082903. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3082903/. 
  141. ↑ Hayashi, M.; Katou, Y.; Itoh, T.; Tazumi, A.; Yamada, Y.; Takahashi, T.; Nakagawa, T.; Shirahige, K. et al. (2007). "Genome-wide localization of pre-RC sites and identification of replication origins in fission yeast". The EMBO Journal 26 (5): 1327–1339. doi:10.1038/sj.emboj.7601585. PMID 17304213. PMC 1817633. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1817633/. 
  142. ↑ 142.0 142.1 Martin, M. M.; Ryan, M.; Kim, R.; Zakas, A. L.; Fu, H.; Lin, C. M.; Reinhold, W. C.; Davis, S. R. et al. (2011). "Genome-wide depletion of replication initiation events in highly transcribed regions". Genome Research 21 (11): 1822–1832. doi:10.1101/gr.124644.111. PMID 21813623. PMC 3205567. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3205567/. 
  143. ↑ Pourkarimi, E.; Bellush, J. M.; Whitehouse, I. (2016). "Spatiotemporal coupling and decoupling of gene transcription with DNA replication origins during embryogenesis in C. Elegans.". eLife 5. doi:10.7554/eLife.21728. PMID 28009254. PMC 5222557. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5222557/. 
  144. ↑ 144.0 144.1 Rodríguez-Martínez, M.; Pinzón, N.; Ghommidh, C.; Beyne, E.; Seitz, H.; Cayrou, C.; Méchali, M. (2017). "The gastrula transition reorganizes replication-origin selection in Caenorhabditis elegans". Nature Structural & Molecular Biology 24 (3): 290–299. doi:10.1038/nsmb.3363. PMID 28112731. 
  145. ↑ 145.0 145.1 Besnard, E.; Babled, A.; Lapasset, L.; Milhavet, O.; Parrinello, H.; Dantec, C.; Marin, J. M.; Lemaitre, J. M. (2012). "Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs". Nature Structural & Molecular Biology 19 (8): 837–844. doi:10.1038/nsmb.2339. PMID 22751019. 
  146. ↑ Delgado, S.; Gómez, M.; Bird, A.; Antequera, F. (1998). "Initiation of DNA replication at CPG islands in mammalian chromosomes". The EMBO Journal 17 (8): 2426–2435. doi:10.1093/emboj/17.8.2426. PMID 9545253. PMC 1170585. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1170585/. 
  147. ↑ Sequeira-Mendes, J.; Díaz-Uriarte, R.; Apedaile, A.; Huntley, D.; Brockdorff, N.; Gómez, M. (2009). "Transcription initiation activity sets replication origin efficiency in mammalian cells". PLOS Genetics 5 (4): e1000446. doi:10.1371/journal.pgen.1000446. PMID 19360092. PMC 2661365. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2661365/. 
  148. ↑ 148.0 148.1 148.2 Kelly, T.; Callegari, A. J. (2019). "Dynamics of DNA replication in a eukaryotic cell". Proceedings of the National Academy of Sciences of the United States of America 116 (11): 4973–4982. doi:10.1073/pnas.1818680116. PMID 30718387. PMC 6421431. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6421431/. 
  149. ↑ Austin, R. J.; Orr-Weaver, T. L.; Bell, S. P. (1999). "Drosophila ORC specifically binds to ACE3, an origin of DNA replication control element". Genes & Development 13 (20): 2639–2649. doi:10.1101/gad.13.20.2639. PMID 10541550. PMC 317108. //www.ncbi.nlm.nih.gov/pmc/articles/PMC317108/. 
  150. ↑ Beall, E. L.; Manak, J. R.; Zhou, S.; Bell, M.; Lipsick, J. S.; Botchan, M. R. (2002). "Role for a Drosophila Myb-containing protein complex in site-specific DNA replication". Nature 420 (6917): 833–837. doi:10.1038/nature01228. PMID 12490953. 
  151. ↑ Beall, E. L.; Bell, M.; Georlette, D.; Botchan, M. R. (2004). "Dm-myb mutant lethality in Drosophila is dependent upon mip130: Positive and negative regulation of DNA replication". Genes & Development 18 (14): 1667–1680. doi:10.1101/gad.1206604. PMID 15256498. PMC 478189. //www.ncbi.nlm.nih.gov/pmc/articles/PMC478189/. 
  152. ↑ Lewis, P. W.; Beall, E. L.; Fleischer, T. C.; Georlette, D.; Link, A. J.; Botchan, M. R. (2004). "Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex". Genes & Development 18 (23): 2929–2940. doi:10.1101/gad.1255204. PMID 15545624. PMC 534653. //www.ncbi.nlm.nih.gov/pmc/articles/PMC534653/. 
  153. ↑ Bosco, G.; Du, W.; Orr-Weaver, T. L. (2001). "DNA replication control through interaction of E2F-RB and the origin recognition complex". Nature Cell Biology 3 (3): 289–295. doi:10.1038/35060086. PMID 11231579. 
  154. ↑ Chuang, R. Y.; Kelly, T. J. (1999). "The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks". Proceedings of the National Academy of Sciences of the United States of America 96 (6): 2656–2661. doi:10.1073/pnas.96.6.2656. PMID 10077566. PMC 15824. //www.ncbi.nlm.nih.gov/pmc/articles/PMC15824/. 
  155. ↑ Balasov, M.; Huijbregts, R. P.; Chesnokov, I. (2007). "Role of the Orc6 protein in origin recognition complex-dependent DNA binding and replication in Drosophila melanogaster". Molecular and Cellular Biology 27 (8): 3143–3153. doi:10.1128/MCB.02382-06. PMID 17283052. PMC 1899928. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1899928/. 
  156. ↑ Tardat, M.; Brustel, J.; Kirsh, O.; Lefevbre, C.; Callanan, M.; Sardet, C.; Julien, E. (2010). "The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells". Nature Cell Biology 12 (11): 1086–1093. doi:10.1038/ncb2113. PMID 20953199. 
  157. ↑ Beck, D. B.; Burton, A.; Oda, H.; Ziegler-Birling, C.; Torres-Padilla, M. E.; Reinberg, D. (2012). "The role of PR-Set7 in replication licensing depends on Suv4-20h". Genes & Development 26 (23): 2580–2589. doi:10.1101/gad.195636.112. PMID 23152447. PMC 3521623. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3521623/. 
  158. ↑ Brustel, J.; Kirstein, N.; Izard, F.; Grimaud, C.; Prorok, P.; Cayrou, C.; Schotta, G.; Abdelsamie, A. F. et al. (2017). "Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication". The EMBO Journal 36 (18): 2726–2741. doi:10.15252/embj.201796541. PMID 28778956. PMC 5599798. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5599798/. 
  159. ↑ Shoaib, M.; Walter, D.; Gillespie, P. J.; Izard, F.; Fahrenkrog, B.; Lleres, D.; Lerdrup, M.; Johansen, J. V. et al. (2018). "Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing". Nature Communications 9 (1): 3704. doi:10.1038/s41467-018-06066-8. PMID 30209253. PMC 6135857. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6135857/. 
  160. ↑ Noguchi, K.; Vassilev, A.; Ghosh, S.; Yates, J. L.; Depamphilis, M. L. (2006). "The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo". The EMBO Journal 25 (22): 5372–5382. doi:10.1038/sj.emboj.7601396. PMID 17066079. PMC 1636626. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1636626/. 
  161. ↑ Shen, Z.; Chakraborty, A.; Jain, A.; Giri, S.; Ha, T.; Prasanth, K. V.; Prasanth, S. G. (2012). "Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation". Molecular and Cellular Biology 32 (15): 3107–3120. doi:10.1128/MCB.00362-12. PMID 22645314. PMC 3434513. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3434513/. 
  162. ↑ Wang, Y.; Khan, A.; Marks, A. B.; Smith, O. K.; Giri, S.; Lin, Y. C.; Creager, R.; MacAlpine, D. M. et al. (2017). "Temporal association of ORCA/LRWD1 to late-firing origins during G1 dictates heterochromatin replication and organization". Nucleic Acids Research 45 (5): 2490–2502. doi:10.1093/nar/gkw1211. PMID 27924004. PMC 5389698. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5389698/. 
  163. ↑ Bartke, T.; Vermeulen, M.; Xhemalce, B.; Robson, S. C.; Mann, M.; Kouzarides, T. (2010). "Nucleosome-interacting proteins regulated by DNA and histone methylation". Cell 143 (3): 470–484. doi:10.1016/j.cell.2010.10.012. PMID 21029866. PMC 3640253. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3640253/. 
  164. ↑ Vermeulen, M.; Eberl, H. C.; Matarese, F.; Marks, H.; Denissov, S.; Butter, F.; Lee, K. K.; Olsen, J. V. et al. (2010). "Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers". Cell 142 (6): 967–980. doi:10.1016/j.cell.2010.08.020. PMID 20850016. 
  165. ↑ Hein, M. Y.; Hubner, N. C.; Poser, I.; Cox, J.; Nagaraj, N.; Toyoda, Y.; Gak, I. A.; Weisswange, I. et al. (2015). "A human interactome in three quantitative dimensions organized by stoichiometries and abundances". Cell 163 (3): 712–723. doi:10.1016/j.cell.2015.09.053. PMID 26496610. 
  166. ↑ Thomae, A. W.; Pich, D.; Brocher, J.; Spindler, M. P.; Berens, C.; Hock, R.; Hammerschmidt, W.; Schepers, A. (2008). "Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins". Proceedings of the National Academy of Sciences of the United States of America 105 (5): 1692–1697. doi:10.1073/pnas.0707260105. PMID 18234858. PMC 2234206. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2234206/. 
  167. ↑ Zhang, Y.; Huang, L.; Fu, H.; Smith, O. K.; Lin, C. M.; Utani, K.; Rao, M.; Reinhold, W. C. et al. (2016). "A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells". Nature Communications 7: 11748. doi:10.1038/ncomms11748. PMID 27272143. PMC 4899857. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4899857/. 
  168. ↑ Bleichert, F.; Leitner, A.; Aebersold, R.; Botchan, M. R.; Berger, J. M. (2018). "Conformational control and DNA-binding mechanism of the metazoan origin recognition complex". Proceedings of the National Academy of Sciences of the United States of America 115 (26): E5906–E5915. doi:10.1073/pnas.1806315115. PMID 29899147. PMC 6042147. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6042147/. 
  169. ↑ Clarey, M. G.; Botchan, M.; Nogales, E. (2008). "Single particle EM studies of the Drosophila melanogaster origin recognition complex and evidence for DNA wrapping". Journal of Structural Biology 164 (3): 241–249. doi:10.1016/j.jsb.2008.08.006. PMID 18824234. PMC 2640233. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2640233/. 
  170. ↑ Lee, D. G.; Bell, S. P. (1997). "Architecture of the yeast origin recognition complex bound to origins of DNA replication". Molecular and Cellular Biology 17 (12): 7159–7168. doi:10.1128/MCB.17.12.7159. PMID 9372948. PMC 232573. //www.ncbi.nlm.nih.gov/pmc/articles/PMC232573/. 
  171. ↑ Riera, A.; Barbon, M.; Noguchi, Y.; Reuter, L. M.; Schneider, S.; Speck, C. (2017). "From structure to mechanism-understanding initiation of DNA replication". Genes & Development 31 (11): 1073–1088. doi:10.1101/gad.298232.117. PMID 28717046. PMC 5538431. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5538431/. 
  172. ↑ Tognetti, S.; Riera, A.; Speck, C. (2015). "Switch on the engine: How the eukaryotic replicative helicase MCM2-7 becomes activated". Chromosoma 124 (1): 13–26. doi:10.1007/s00412-014-0489-2. PMID 25308420. 
  173. ↑ Berbenetz, N. M.; Nislow, C.; Brown, G. W. (2010). "Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure". PLOS Genetics 6 (9): e1001092. doi:10.1371/journal.pgen.1001092. PMID 20824081. PMC 2932696. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2932696/. 
  174. ↑ Eaton, M. L.; Galani, K.; Kang, S.; Bell, S. P.; MacAlpine, D. M. (2010). "Conserved nucleosome positioning defines replication origins". Genes & Development 24 (8): 748–753. doi:10.1101/gad.1913210. PMID 20351051. PMC 2854390. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2854390/. 
  175. ↑ 175.0 175.1 Azmi, I. F.; Watanabe, S.; Maloney, M. F.; Kang, S.; Belsky, J. A.; MacAlpine, D. M.; Peterson, C. L.; Bell, S. P. (2017). "Nucleosomes influence multiple steps during replication initiation". eLife 6. doi:10.7554/eLife.22512. PMID 28322723. PMC 5400510. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5400510/. 
  176. ↑ Miotto, B.; Struhl, K. (2010). "HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin". Molecular Cell 37 (1): 57–66. doi:10.1016/j.molcel.2009.12.012. PMID 20129055. PMC 2818871. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2818871/. 
  177. ↑ Liu, J.; Zimmer, K.; Rusch, D. B.; Paranjape, N.; Podicheti, R.; Tang, H.; Calvi, B. R. (2015). "DNA sequence templates adjacent nucleosome and ORC sites at gene amplification origins in Drosophila". Nucleic Acids Research 43 (18): 8746–8761. doi:10.1093/nar/gkv766. PMID 26227968. PMC 4605296. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4605296/. 
  178. ↑ Zhao, P. A.; Rivera-Mulia, J. C.; Gilbert, D. M. (2017). "Replication Domains: Genome Compartmentalization into Functional Replication Units". Advances in Experimental Medicine and Biology 1042: 229–257. doi:10.1007/978-981-10-6955-0_11. ISBN 978-981-10-6954-3. PMID 29357061. 
  179. ↑ Sugimoto, N.; Fujita, M. (2017). "Molecular Mechanism for Chromatin Regulation During MCM Loading in Mammalian Cells". Advances in Experimental Medicine and Biology 1042: 61–78. doi:10.1007/978-981-10-6955-0_3. ISBN 978-981-10-6954-3. PMID 29357053. 
  180. ↑ MacAlpine, D. M.; Almouzni, G. (2013). "Chromatin and DNA replication". Cold Spring Harbor Perspectives in Biology 5 (8): a010207. doi:10.1101/cshperspect.a010207. PMID 23751185. PMC 3721285. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3721285/. 
  181. ↑ Sima, J.; Chakraborty, A.; Dileep, V.; Michalski, M.; Klein, K. N.; Holcomb, N. P.; Turner, J. L.; Paulsen, M. T. et al. (2019). "Identifying cis Elements for Spatiotemporal Control of Mammalian DNA Replication". Cell 176 (4): 816–830.e18. doi:10.1016/j.cell.2018.11.036. PMID 30595451. PMC 6546437. //www.ncbi.nlm.nih.gov/pmc/articles/PMC6546437/. 
  182. ↑ Cadoret, J. C.; Meisch, F.; Hassan-Zadeh, V.; Luyten, I.; Guillet, C.; Duret, L.; Quesneville, H.; Prioleau, M. N. (2008). "Genome-wide studies highlight indirect links between human replication origins and gene regulation". Proceedings of the National Academy of Sciences of the United States of America 105 (41): 15837–15842. doi:10.1073/pnas.0805208105. PMID 18838675. PMC 2572913. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2572913/. 
  183. ↑ Gros, J.; Kumar, C.; Lynch, G.; Yadav, T.; Whitehouse, I.; Remus, D. (2015). "Post-licensing Specification of Eukaryotic Replication Origins by Facilitated Mcm2-7 Sliding along DNA". Molecular Cell 60 (5): 797–807. doi:10.1016/j.molcel.2015.10.022. PMID 26656162. PMC 4680849. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4680849/. 
  184. ↑ Letessier, A.; Millot, G. A.; Koundrioukoff, S.; Lachagès, A. M.; Vogt, N.; Hansen, R. S.; Malfoy, B.; Brison, O. et al. (2011). "Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site". Nature 470 (7332): 120–123. doi:10.1038/nature09745. PMID 21258320. 
  185. ↑ 185.0 185.1 Smith, O. K.; Kim, R.; Fu, H.; Martin, M. M.; Lin, C. M.; Utani, K.; Zhang, Y.; Marks, A. B. et al. (2016). "Distinct epigenetic features of differentiation-regulated replication origins". Epigenetics & Chromatin 9: 18. doi:10.1186/s13072-016-0067-3. PMID 27168766. PMC 4862150. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4862150/. 
  186. ↑ Sher, N.; Bell, G. W.; Li, S.; Nordman, J.; Eng, T.; Eaton, M. L.; MacAlpine, D. M.; Orr-Weaver, T. L. (2012). "Developmental control of gene copy number by repression of replication initiation and fork progression". Genome Research 22 (1): 64–75. doi:10.1101/gr.126003.111. PMID 22090375. PMC 3246207. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3246207/. 
  187. ↑ Comoglio, F.; Schlumpf, T.; Schmid, V.; Rohs, R.; Beisel, C.; Paro, R. (2015). "High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins". Cell Reports 11 (5): 821–834. doi:10.1016/j.celrep.2015.03.070. PMID 25921534. PMC 4562395. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4562395/. 
  188. ↑ Calvi, B. R.; Lilly, M. A.; Spradling, A. C. (1998). "Cell cycle control of chorion gene amplification". Genes & Development 12 (5): 734–744. doi:10.1101/gad.12.5.734. PMID 9499407. PMC 316579. //www.ncbi.nlm.nih.gov/pmc/articles/PMC316579/. 
  189. ↑ Mosig, G. (1998). "Recombination and recombination-dependent DNA replication in bacteriophage T4". Annual Review of Genetics 32: 379–413. doi:10.1146/annurev.genet.32.1.379. PMID 9928485. 
  190. ↑ Ravoitytė, B.; Wellinger, R. E. (2017). "Non-Canonical Replication Initiation: You're Fired!". Genes 8 (2): 54. doi:10.3390/genes8020054. PMID 28134821. PMC 5333043. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5333043/. 
  191. ↑ Asai, T.; Sommer, S.; Bailone, A.; Kogoma, T. (1993). "Homologous recombination-dependent initiation of DNA replication from DNA damage-inducible origins in Escherichia coli". The EMBO Journal 12 (8): 3287–3295. doi:10.1002/j.1460-2075.1993.tb05998.x. PMID 8344265. PMC 413596. //www.ncbi.nlm.nih.gov/pmc/articles/PMC413596/. 
  192. ↑ Lydeard, J. R.; Jain, S.; Yamaguchi, M.; Haber, J. E. (2007). "Break-induced replication and telomerase-independent telomere maintenance require Pol32". Nature 448 (7155): 820–823. doi:10.1038/nature06047. PMID 17671506. 
  193. ↑ Dasgupta, S.; Masukata, H.; Tomizawa, J. (1987). "Multiple mechanisms for initiation of ColE1 DNA replication: DNA synthesis in the presence and absence of ribonuclease H". Cell 51 (6): 1113–1122. doi:10.1016/0092-8674(87)90597-6. PMID 2446774. 
  194. ↑ Stuckey, R.; García-Rodríguez, N.; Aguilera, A.; Wellinger, R. E. (2015). "Role for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system". Proceedings of the National Academy of Sciences of the United States of America 112 (18): 5779–5784. doi:10.1073/pnas.1501769112. PMID 25902524. PMC 4426422. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4426422/. 
  195. ↑ Burki, F. (2014). "The eukaryotic tree of life from a global phylogenomic perspective". Cold Spring Harbor Perspectives in Biology 6 (5): a016147. doi:10.1101/cshperspect.a016147. PMID 24789819. PMC 3996474. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3996474/. 
  196. ↑ Lee, P. H.; Meng, X.; Kapler, G. M. (2015). "Developmental regulation of the Tetrahymena thermophila origin recognition complex". PLOS Genetics 11 (1): e1004875. doi:10.1371/journal.pgen.1004875. PMID 25569357. PMC 4287346. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4287346/. 
  197. ↑ Mohammad, M. M.; Donti, T. R.; Sebastian Yakisich, J.; Smith, A. G.; Kapler, G. M. (2007). "Tetrahymena ORC contains a ribosomal RNA fragment that participates in rDNA origin recognition". The EMBO Journal 26 (24): 5048–5060. doi:10.1038/sj.emboj.7601919. PMID 18007594. PMC 2140106. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2140106/. 
  198. ↑ Donti, T. R.; Datta, S.; Sandoval, P. Y.; Kapler, G. M. (2009). "Differential targeting of Tetrahymena ORC to ribosomal DNA and non-rDNA replication origins". The EMBO Journal 28 (3): 223–233. doi:10.1038/emboj.2008.282. PMID 19153611. PMC 2637336. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2637336/. 
  199. ↑ Marques, C. A.; McCulloch, R. (2018). "Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes". Current Genomics 19 (2): 98–109. doi:10.2174/1389202918666170815144627. PMID 29491738. PMC 5814967. //www.ncbi.nlm.nih.gov/pmc/articles/PMC5814967/. 
  200. ↑ Marques, C. A.; Tiengwe, C.; Lemgruber, L.; Damasceno, J. D.; Scott, A.; Paape, D.; Marcello, L.; McCulloch, R. (2016). "Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation". Nucleic Acids Research 44 (10): 4763–4784. doi:10.1093/nar/gkw147. PMID 26951375. PMC 4889932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4889932/. 
  201. ↑ Tiengwe, C.; Marcello, L.; Farr, H.; Gadelha, C.; Burchmore, R.; Barry, J. D.; Bell, S. D.; McCulloch, R. (2012). "Identification of ORC1/CDC6-interacting factors in Trypanosoma brucei reveals critical features of origin recognition complex architecture". PLOS ONE 7 (3): e32674. doi:10.1371/journal.pone.0032674. PMID 22412905. PMC 3297607. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3297607/. 
  202. ↑ Marques, C. A.; Dickens, N. J.; Paape, D.; Campbell, S. J.; McCulloch, R. (2015). "Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe". Genome Biology 16: 230. doi:10.1186/s13059-015-0788-9. PMID 26481451. PMC 4612428. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4612428/. 
Retrieved from "https://en.wikiversity.org/w/index.php?title=PLOS/Origins_of_DNA_Replication&oldid=2360178"