replication origin


Summary: A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

Top Publications

  1. Hizume K, Yagura M, Araki H. Concerted interaction between origin recognition complex (ORC), nucleosomes and replication origin DNA ensures stable ORC-origin binding. Genes Cells. 2013;18:764-79 pubmed publisher
    ..Moreover, stable binding of ORC to chromatin requires linker DNA. Thus, ORC establishes its interaction with origin by binding to both nucleosome-free origin DNA and neighboring nucleosomes...
  2. Martin M, Ryan M, Kim R, Zakas A, Fu H, Lin C, et al. Genome-wide depletion of replication initiation events in highly transcribed regions. Genome Res. 2011;21:1822-32 pubmed publisher
    ..Data presented here identify replication initiation sites throughout the genome, providing a foundation for further analyses of DNA-replication dynamics and cell-cycle progression. ..
  3. Crevel G, Cotterill S. Forced binding of the origin of replication complex to chromosomal sites in Drosophila S2 cells creates an origin of replication. J Cell Sci. 2012;125:965-72 pubmed publisher
    ..We expect that this system can provide a useful tool for the study of site-specific events at origins of replication in higher eukaryotes and a means to dissect Orc-dependent and Orc-independent events at origins. ..
  4. Pinto U, Flores Mireles A, Costa E, Winans S. RepC protein of the octopine-type Ti plasmid binds to the probable origin of replication within repC and functions only in cis. Mol Microbiol. 2011;81:1593-606 pubmed publisher
    ..Here we show that the replication origin of an Agrobacterium tumefaciens Ti plasmid resides fully within its repC gene...
  5. Siow C, Nieduszynska S, Müller C, Nieduszynski C. OriDB, the DNA replication origin database updated and extended. Nucleic Acids Res. 2012;40:D682-6 pubmed publisher is a database containing collated genome-wide mapping studies of confirmed and predicted replication origin sites. The original database collated and curated Saccharomyces cerevisiae origin mapping studies...
  6. Costas C, de la Paz Sanchez M, Stroud H, Yu Y, Oliveros J, Feng S, et al. Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks. Nat Struct Mol Biol. 2011;18:395-400 pubmed publisher
    ..Z, H3K4me2, H3K4me3 and H4K5ac, and depleted in H3K4me1 and H3K9me2. Our data help clarify the epigenetic specification of DNA replication origins in A. thaliana and have implications for other eukaryotes. ..
  7. Wang X, Lesterlin C, Reyes Lamothe R, Ball G, Sherratt D. Replication and segregation of an Escherichia coli chromosome with two replication origins. Proc Natl Acad Sci U S A. 2011;108:E243-50 pubmed publisher
    ..Characterized bacteria, unlike eukaryotes and some archaea, initiate replication bidirectionally from a single replication origin contained within a circular or linear chromosome...
  8. Koch B, Ma X, Løbner Olesen A. Replication of Vibrio cholerae chromosome I in Escherichia coli: dependence on dam methylation. J Bacteriol. 2010;192:3903-14 pubmed publisher
    ..This is supported by the fact that the requirement for dam can be alleviated by increasing negative supercoiling of the chromosome through oversupply of the DNA gyrase or loss of SeqA activity. ..
  9. Cervantes Rivera R, Pedraza López F, Pérez Segura G, Cevallos M. The replication origin of a repABC plasmid. BMC Microbiol. 2011;11:158 pubmed publisher
    ..RepC can act as an incompatibility factor, and the last 39 amino acid residues of the carboxy-terminal region of this protein are involved in promoting this phenotype. ..

More Information


  1. Hayano M, Kanoh Y, Matsumoto S, Masai H. Mrc1 marks early-firing origins and coordinates timing and efficiency of initiation in fission yeast. Mol Cell Biol. 2011;31:2380-91 pubmed publisher
    ..We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein. ..
  2. Sugimoto N, Yugawa T, Iizuka M, Kiyono T, Fujita M. Chromatin remodeler sucrose nonfermenting 2 homolog (SNF2H) is recruited onto DNA replication origins through interaction with Cdc10 protein-dependent transcript 1 (Cdt1) and promotes pre-replication complex formation. J Biol Chem. 2011;286:39200-10 pubmed publisher
    ..Because efficient loading of excess MCM complexes is thought to be required for cells to tolerate replication stress, Cdt1- and SNF2H-mediated promotion of MCM loading may be biologically relevant for the regulation of DNA replication. ..
  3. Liu J, MCCONNELL K, Dixon M, Calvi B. Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex. Mol Biol Cell. 2012;23:200-12 pubmed publisher
    ..Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. ..
  4. Taylor M, Moore K, Murray J, Aves S, Price C. Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1). DNA Repair (Amst). 2011;10:1154-63 pubmed publisher
    ..Comparison of the levels of chromatin association at origins of replication and stalled replication forks and the differential requirement for Rad9 suggest functional differences for Rad4(TopBP1) at these distinct sites. ..
  5. Lubelsky Y, Sasaki T, Kuipers M, Lucas I, Le Beau M, Carignon S, et al. Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone. Nucleic Acids Res. 2011;39:3141-55 pubmed publisher
  6. Wong P, Winter S, Zaika E, Cao T, Oguz U, Koomen J, et al. Cdc45 limits replicon usage from a low density of preRCs in mammalian cells. PLoS ONE. 2011;6:e17533 pubmed publisher
    ..The stable, continuous, and rate-limiting nature of Cdc45 suggests that Cdc45 contributes to the staggering of replicon usage throughout S-phase, and that replicon activation requires reutilization of existing Cdc45 during S-phase. ..
  7. Dueber E, Costa A, Corn J, Bell S, Berger J. Molecular determinants of origin discrimination by Orc1 initiators in archaea. Nucleic Acids Res. 2011;39:3621-31 pubmed publisher
    ..Our results show that both the WHD and ATPase region influence origin recognition by Orc1/Cdc6, and suggest that not only DNA sequence, but also local DNA structure help define archaeal initiator binding sites. ..
  8. Ge X, Blow J. Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories. J Cell Biol. 2010;191:1285-97 pubmed publisher
    ..This minimizes the deleterious consequences of fork stalling and prevents similar problems from arising in unreplicated regions of the genome. ..
  9. Lang S, Kirchberger P, Gruber C, Redzej A, Raffl S, Zellnig G, et al. An activation domain of plasmid R1 TraI protein delineates stages of gene transfer initiation. Mol Microbiol. 2011;82:1071-85 pubmed publisher
    ..Related plasmid F adapted to R17 independently of TraI. It follows that selection for phage resistance drives not only variation in TraA pilins but diversifies TraD and its binding partners in a plasmid-specific manner. ..
  10. Di Rienzi S, Lindstrom K, Mann T, Noble W, Raghuraman M, Brewer B. Maintaining replication origins in the face of genomic change. Genome Res. 2012;22:1940-52 pubmed publisher
    ..We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved...
  11. Liu C, Chang J, Ma C, Li L, Zhou S. Mitochondrial genomes of two Sinochlora species (Orthoptera): novel genome rearrangements and recognition sequence of replication origin. BMC Genomics. 2013;14:114 pubmed publisher
    ..remains regarding whether a long thymine-nucleotide stretch (T-stretch) involved in the recognition of the replication origin exists in the control region (CR) of Orthoptera mitochondrial DNA (mtDNA)...
  12. Hoggard T, Shor E, Müller C, Nieduszynski C, Fox C. A Link between ORC-origin binding mechanisms and origin activation time revealed in budding yeast. PLoS Genet. 2013;9:e1003798 pubmed publisher
    ..These data reveal a novel association between ORC-origin binding mechanisms and the regulation of origin activation time. ..
  13. Watase G, Takisawa H, Kanemaki M. Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Curr Biol. 2012;22:343-9 pubmed publisher
    ..Thus, Mcm10 plays an essential role in functioning of the CMG replicative helicase independent of assembly of a stable CMG complex at origins. ..
  14. Scholefield G, Errington J, Murray H. Soj/ParA stalls DNA replication by inhibiting helix formation of the initiator protein DnaA. EMBO J. 2012;31:1542-55 pubmed publisher
    ..oligomer built upon interactions between neighbouring AAA+ domains, that in vitro stretches DNA to promote replication origin opening...
  15. Skarstad K, Katayama T. Regulating DNA replication in bacteria. Cold Spring Harb Perspect Biol. 2013;5:a012922 pubmed publisher
    The replication origin and the initiator protein DnaA are the main targets for regulation of chromosome replication in bacteria. The origin bears multiple DnaA binding sites, while DnaA contains ATP/ADP-binding and DNA-binding domains...
  16. Duan Z, Andronescu M, Schutz K, McIlwain S, Kim Y, Lee C, et al. A three-dimensional model of the yeast genome. Nature. 2010;465:363-7 pubmed publisher
    ..Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome...
  17. Zegerman P, Diffley J. Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation. Nature. 2010;467:474-8 pubmed publisher
    ..Our results explain how checkpoints regulate origin firing and demonstrate that the slowing of S phase by the 'intra-S checkpoint' is primarily due to the inhibition of origin firing. ..
  18. Gerhold J, Aun A, Sedman T, Jõers P, Sedman J. Strand invasion structures in the inverted repeat of Candida albicans mitochondrial DNA reveal a role for homologous recombination in replication. Mol Cell. 2010;39:851-61 pubmed publisher
    ..We provide topological evidence for recombination-driven mtDNA replication initiation and introduce C. albicans as a suitable model organism to study wild-type mtDNA maintenance in yeast. ..
  19. Flynn K, Vohr S, Hatcher P, Cooper V. Evolutionary rates and gene dispensability associate with replication timing in the archaeon Sulfolobus islandicus. Genome Biol Evol. 2010;2:859-69 pubmed publisher
    ..Therefore, in this genus of Archaea as well as in many Bacteria, evolutionary rates and variation in genome content associate with replication timing. ..
  20. Liu G, Chen X, Bissler J, Sinden R, Leffak M. Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human cells. Nat Chem Biol. 2010;6:652-9 pubmed publisher
    ..lines in which (CTG) x (CAG) repeats are replicated from an ectopic copy of the Myc (also known as c-myc) replication origin. In this system, the tendency of chromosomal (CTG) x (CAG) tracts to expand or contract was affected by ..
  21. Dellarole M, Sánchez I, de Prat Gay G. Thermodynamics of cooperative DNA recognition at a replication origin and transcription regulatory site. Biochemistry. 2010;49:10277-86 pubmed publisher
    ..This is in surprising agreement with previous results for this domain, which revealed a strong coupling between global dynamics and DNA recognition. ..
  22. Tanaka S, Araki H. Multiple regulatory mechanisms to inhibit untimely initiation of DNA replication are important for stable genome maintenance. PLoS Genet. 2011;7:e1002136 pubmed publisher
    ..These findings highlight the importance of having multiple inhibitory mechanisms to prevent the untimely initiation of chromosome replication to preserve stable genome maintenance over generations in eukaryotes. ..
  23. Karschau J, Blow J, de Moura A. Optimal placement of origins for DNA replication. Phys Rev Lett. 2012;108:058101 pubmed
    ..We show that under some conditions the minimization of replication time leads to the grouping of origins, and relate this to experimental data in a number of species showing origin grouping. ..
  24. Mesner L, Valsakumar V, Karnani N, Dutta A, Hamlin J, Bekiranov S. Bubble-chip analysis of human origin distributions demonstrates on a genomic scale significant clustering into zones and significant association with transcription. Genome Res. 2011;21:377-89 pubmed publisher
    ..In addition, HeLa and GM06990 cells activate remarkably different origin populations. Finally, there is only moderate concordance between the log-phase HeLa bubble map and published maps of small nascent strands for this cell line. ..
  25. Karnani N, Dutta A. The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes Dev. 2011;25:621-33 pubmed publisher
  26. Boos D, Yekezare M, Diffley J. Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science. 2013;340:981-4 pubmed publisher
    ..We propose that MTBP acts with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells. ..
  27. Nagata Y, Natsui S, Endo R, Ohtsubo Y, Ichikawa N, Ankai A, et al. Genomic organization and genomic structural rearrangements of Sphingobium japonicum UT26, an archetypal ?-hexachlorocyclohexane-degrading bacterium. Enzyme Microb Technol. 2011;49:499-508 pubmed publisher
    ..These facts strongly suggest that IS6100 plays important roles both in the dissemination of the specific lin genes and in the genome rearrangements...
  28. Stelter M, Gutsche I, Kapp U, Bazin A, Bajic G, Goret G, et al. Architecture of a dodecameric bacterial replicative helicase. Structure. 2012;20:554-64 pubmed publisher
    ..The HpDnaB double-hexamer architecture supports an alternative strategy to load bacterial helicases onto forks in the absence of helicase loaders. ..
  29. Pan L, Leung P, Gu J. A new ColE1-like plasmid group revealed by comparative analysis of the replication proficient fragments of Vibrionaceae plasmids. J Microbiol Biotechnol. 2010;20:1163-78 pubmed
    ..All the results indicated that the 15 plasmids form a new ColE1-like group, providing basis for rapid characterization and classification of Vibrionaceae plasmids...
  30. Berbenetz N, Nislow C, Brown G. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure. PLoS Genet. 2010;6:e1001092 pubmed publisher
    ..occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers) positions nucleosomes adjacent to the origin to promote replication origin function.
  31. Müller C, Nieduszynski C. Conservation of replication timing reveals global and local regulation of replication origin activity. Genome Res. 2012;22:1953-62 pubmed publisher
    ..cerevisiae/S. bayanus hybrid strain and find that there are both local and global regulators of origin function. ..
  32. Lian H, Robertson E, Hiraga S, Alvino G, Collingwood D, McCune H, et al. The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation. Mol Biol Cell. 2011;22:1753-65 pubmed publisher
  33. Liachko I, Youngblood R, Keich U, Dunham M. High-resolution mapping, characterization, and optimization of autonomously replicating sequences in yeast. Genome Res. 2013;23:698-704 pubmed publisher
    ..The yeast autonomously replicating sequence (ARS) assay has been a valuable tool in dissecting replication origin structure and function...
  34. Frigola J, Remus D, Mehanna A, Diffley J. ATPase-dependent quality control of DNA replication origin licensing. Nature. 2013;495:339-43 pubmed publisher
    ..Our work provides new insights into how origins are licensed and reveals a novel ATPase-dependent mechanism contributing to precise once per cell cycle replication. ..
  35. Errico A, Costanzo V. Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol. 2012;47:222-35 pubmed publisher
    ..Here, we discuss the specific contribution of these factors in preserving fork structure and ensuring accurate completion of DNA replication. ..
  36. Duderstadt K, Berger J. A structural framework for replication origin opening by AAA+ initiation factors. Curr Opin Struct Biol. 2013;23:144-53 pubmed publisher
    ..Comparative studies between initiation systems in turn provide clues as to how duplex origin regions may be melted during initiation events. ..
  37. Miyabe I, Kunkel T, Carr A. The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet. 2011;7:e1002407 pubmed publisher
    ..base substitutions in reporter genes placed in opposite orientations relative to a well-characterized replication origin are strand-specific and distributed in patterns implying that Pol? is primarily involved in lagging strand ..
  38. Chandok G, Kapoor K, Brick R, Sidorova J, Krasilnikova M. A distinct first replication cycle of DNA introduced in mammalian cells. Nucleic Acids Res. 2011;39:2103-15 pubmed publisher
    ..This work demonstrates, for the first time, differences in the replication progression during the first and subsequent replication cycles in mammalian cells...
  39. de Moura A, Retkute R, Hawkins M, Nieduszynski C. Mathematical modelling of whole chromosome replication. Nucleic Acids Res. 2010;38:5623-33 pubmed publisher
    ..In summary, we demonstrate that a stochastic model can recapitulate experimental observations, including those that might be interpreted as deterministic such as ordered origin activation times. ..
  40. Marsolier Kergoat M. Asymmetry indices for analysis and prediction of replication origins in eukaryotic genomes. PLoS ONE. 2012;7:e45050 pubmed publisher
    ..However, I show here that the skew jumps at C. albicans centromeres are not related to replication and that replication-associated GC and TA skews in C. albicans have in fact the opposite directions of what was proposed. ..
  41. Chang F, May C, Hoggard T, Miller J, Fox C, Weinreich M. High-resolution analysis of four efficient yeast replication origins reveals new insights into the ORC and putative MCM binding elements. Nucleic Acids Res. 2011;39:6523-35 pubmed publisher
  42. Blitzblau H, Chan C, Hochwagen A, Bell S. Separation of DNA replication from the assembly of break-competent meiotic chromosomes. PLoS Genet. 2012;8:e1002643 pubmed publisher
    ..The functional separation of these processes reveals a modular method of building meiotic chromosomes and predicts that any crosstalk between these modules must occur through superimposed regulatory mechanisms. ..
  43. Hayano M, Kanoh Y, Matsumoto S, Renard Guillet C, Shirahige K, Masai H. Rif1 is a global regulator of timing of replication origin firing in fission yeast. Genes Dev. 2012;26:137-50 pubmed publisher
    ..Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes. ..
  44. Nitharwal R, Verma V, Dasgupta S, Dhar S. Helicobacter pylori chromosomal DNA replication: current status and future perspectives. FEBS Lett. 2011;585:7-17 pubmed publisher
    ..These differences suggest different mechanisms of DNA replication at initiation and restart of stalled forks in H. pylori. ..
  45. Letessier A, Millot G, Koundrioukoff S, Lachages A, Vogt N, Hansen R, et al. Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature. 2011;470:120-3 pubmed publisher
    ..Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates...
  46. Hayes S, Horbay M, Hayes C. A CI-independent form of replicative inhibition: turn off of early replication of bacteriophage lambda. PLoS ONE. 2012;7:e36498 pubmed publisher
    ..Our results for plasmid based IP suggest the hypothesis that there is a natural mechanism for silencing early theta-mode replication initiation, i.e. the buildup of ? genomes with oop(+)ori?(+) sequence...
  47. Dellino G, Cittaro D, Piccioni R, Luzi L, Banfi S, Segalla S, et al. Genome-wide mapping of human DNA-replication origins: levels of transcription at ORC1 sites regulate origin selection and replication timing. Genome Res. 2013;23:1-11 pubmed publisher
    ..These findings are compatible with a scenario whereby TSS expression levels influence the efficiency of ORC1 recruitment at G(1) and the probability of firing during S. ..
  48. Cayrou C, Coulombe P, Puy A, Rialle S, Kaplan N, Segal E, et al. New insights into replication origin characteristics in metazoans. Cell Cycle. 2012;11:658-67 pubmed publisher
    ..Finally, OGREs predict G-quadruplex structures at Oris that might be structural elements controlling the choice or activation of replication origins. ..
  49. Labib K, De Piccoli G. Surviving chromosome replication: the many roles of the S-phase checkpoint pathway. Philos Trans R Soc Lond B Biol Sci. 2011;366:3554-61 pubmed publisher
    ..This review considers some of the key experiments that have led to our current understanding of this highly complex pathway. ..
  50. Mantiero D, Mackenzie A, Donaldson A, Zegerman P. Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J. 2011;30:4805-14 pubmed publisher
  51. Stokke C, Waldminghaus T, Skarstad K. Replication patterns and organization of replication forks in Vibrio cholerae. Microbiology. 2011;157:695-708 pubmed publisher
    ..The increased degree of fork organization during rapid growth may be a means by which correct segregation of daughter molecules is facilitated. ..
  52. Rudolph C, Upton A, Stockum A, Nieduszynski C, Lloyd R. Avoiding chromosome pathology when replication forks collide. Nature. 2013;500:608-11 pubmed publisher
    ..The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome. ..
  53. Dimitrova D. DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci. J Cell Sci. 2011;124:2743-52 pubmed publisher