dna replication timing


Summary: The temporal order in which the DNA of the GENOME is replicated.

Top Publications

  1. Liu L, De S, Michor F. DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes. Nat Commun. 2013;4:1502 pubmed publisher
    ..determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features...
  2. Hiratani I, Takebayashi S, Lu J, Gilbert D. Replication timing and transcriptional control: beyond cause and effect--part II. Curr Opin Genet Dev. 2009;19:142-9 pubmed publisher
  3. Pope B, Tsumagari K, Battaglia D, Ryba T, Hiratani I, Ehrlich M, et al. DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy. PLoS ONE. 2011;6:e27413 pubmed publisher
    ..2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing ..
  4. Desprat R, Thierry Mieg D, Lailler N, Lajugie J, Schildkraut C, Thierry Mieg J, et al. Predictable dynamic program of timing of DNA replication in human cells. Genome Res. 2009;19:2288-99 pubmed publisher
  5. Cerrato F, Dean W, Davies K, Kagotani K, Mitsuya K, Okumura K, et al. Paternal imprints can be established on the maternal Igf2-H19 locus without altering replication timing of DNA. Hum Mol Genet. 2003;12:3123-32 pubmed
    ..include differential DNA methylation, histone acetylation and methylation, subnuclear localization and DNA replication timing. While DNA methylation has been shown to be necessary both for establishment and maintenance of imprinting,..
  6. Chen C, Rappailles A, Duquenne L, Huvet M, Guilbaud G, Farinelli L, et al. Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome Res. 2010;20:447-57 pubmed publisher
    ..Similar results are observed in the mouse, which indicates that replication timing is a main factor affecting nucleotide substitution dynamics at non-CpG sites and constitutes a major neutral process driving mammalian genome evolution. ..
  7. Donley N, Thayer M. DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability. Semin Cancer Biol. 2013;23:80-9 pubmed publisher
    ..Aberrant DNA replication timing is associated with changes in gene expression, changes in epigenetic modifications and an increased ..
  8. Janoueix Lerosey I, Hupe P, Maciorowski Z, La Rosa P, Schleiermacher G, Pierron G, et al. Preferential occurrence of chromosome breakpoints within early replicating regions in neuroblastoma. Cell Cycle. 2005;4:1842-6 pubmed
    ..These results unambiguously establish a link between unbalanced translocations, whose most likely mechanism of occurrence relies on break-induced replication, and early replication of the genome. ..
  9. Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214-218 pubmed publisher
    ..and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity...

More Information


  1. Perry P, Sauer S, Billon N, Richardson W, Spivakov M, Warnes G, et al. A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction. Cell Cycle. 2004;3:1645-50 pubmed
    ..These results show that loss of pluripotency (and lineage choice) is associated with extensive and predictable changes in the replication timing of key regulator genes. ..
  2. White E, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley E, et al. DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci U S A. 2004;101:17771-6 pubmed
    ..Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program. ..
  3. Diffley J. Regulation of early events in chromosome replication. Curr Biol. 2004;14:R778-86 pubmed
    ..Geminin plays a crucial role in inhibiting licensing in metazoans and, like cyclins, is inactivated by the APC/C. Strategies involved in preventing re-replication in different organisms will be discussed. ..
  4. Rhind N, Gilbert D. DNA replication timing. Cold Spring Harb Perspect Biol. 2013;5:a010132 pubmed publisher
    ..Whether these patterns have inherent biological functions or simply reflect higher-order genome structure is an open question. ..
  5. Yang F, Shao C, Vedanarayanan V, Ehrlich M. Cytogenetic and immuno-FISH analysis of the 4q subtelomeric region, which is associated with facioscapulohumeral muscular dystrophy. Chromosoma. 2004;112:350-9 pubmed
    ..2 regions of FSHD myoblasts did not behave differently than those of control myoblasts. Other models for how D4Z4 array contraction causes long-distance regulation of gene expression in cis need to be tested. ..
  6. Gilbert D, Takebayashi S, Ryba T, Lu J, Pope B, Wilson K, et al. Space and time in the nucleus: developmental control of replication timing and chromosome architecture. Cold Spring Harb Symp Quant Biol. 2010;75:143-53 pubmed publisher
  7. Yang S, Rhind N, Bechhoefer J. Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing. Mol Syst Biol. 2010;6:404 pubmed publisher
    ..This model is the first to suggest a detailed, testable, biochemically plausible mechanism for the regulation of replication timing in eukaryotes. ..
  8. Claycomb J, Benasutti M, Bosco G, Fenger D, Orr Weaver T. Gene amplification as a developmental strategy: isolation of two developmental amplicons in Drosophila. Dev Cell. 2004;6:145-55 pubmed
    ..Thus, during follicle cell differentiation the entire genome is overreplicated as the cells become polyploid, and subsequently specific genomic intervals are overreplicated to facilitate gene expression. ..
  9. 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. ..
  10. Koren A, Soifer I, Barkai N. MRC1-dependent scaling of the budding yeast DNA replication timing program. Genome Res. 2010;20:781-90 pubmed publisher
    We describe the DNA replication timing programs of 14 yeast mutants with an extended S phase identified by a novel genome-wide screen...
  11. Shufaro Y, Lacham Kaplan O, Tzuberi B, McLaughlin J, Trounson A, Cedar H, et al. Reprogramming of DNA replication timing. Stem Cells. 2010;28:443-9 pubmed publisher
    ..Taken together, these results suggest that, unlike DNA methylation, the molecular mechanisms governing replication timing are not only stable but can also be easily reprogrammed. ..
  12. 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
  13. Hiratani I, Ryba T, Itoh M, Rathjen J, Kulik M, Papp B, et al. Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis. Genome Res. 2010;20:155-69 pubmed publisher
  14. 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. ..
  15. Rampakakis E, Di Paola D, Chan M, Zannis Hadjopoulos M. Dynamic changes in chromatin structure through post-translational modifications of histone H3 during replication origin activation. J Cell Biochem. 2009;108:400-7 pubmed publisher
    ..These results suggest that specific histone modifications are associated with origin firing, temporal activation and replication fork progression and underscore the importance of species specificity. ..
  16. Karnani N, Taylor C, Dutta A. Microarray analysis of DNA replication timing. Methods Mol Biol. 2009;556:191-203 pubmed publisher
    ..These transition zones can play a significant role in identifying insulators that separate chromosomal domains with different chromatin modifications. ..
  17. Schwaiger M, Stadler M, Bell O, Kohler H, Oakeley E, Schübeler D. Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome. Genes Dev. 2009;23:589-601 pubmed publisher
    ..Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription. ..
  18. Ryba T, Hiratani I, Sasaki T, Battaglia D, Kulik M, Zhang J, et al. Replication timing: a fingerprint for cell identity and pluripotency. PLoS Comput Biol. 2011;7:e1002225 pubmed publisher
    ..In sum, replication fingerprints provide a comprehensive means for cell characterization and are a promising tool for identifying regions with cell type-specific organization. ..
  19. De S, Michor F. DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nat Biotechnol. 2011;29:1103-8 pubmed publisher
    ..Here we integrate data on DNA replication timing, long-range interactions between genomic material, and 331,724 SCNAs from 2,792 cancer samples classified ..
  20. 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. ..
  21. Azuara V. Profiling of DNA replication timing in unsynchronized cell populations. Nat Protoc. 2006;1:2171-7 pubmed
    ..Here I describe in detail the DNA replication timing method, whereby unsynchronized cell populations are pulse-labeled with 5-bromo-2'-deoxyuridine (BrdU), ..
  22. Rhind N. DNA replication timing: random thoughts about origin firing. Nat Cell Biol. 2006;8:1313-6 pubmed
    ..This model assumes varying origin efficiency instead of a strict origin-timing programme. Here, we discuss the evidence for both models. ..
  23. Aparicio O. Location, location, location: it's all in the timing for replication origins. Genes Dev. 2013;27:117-28 pubmed publisher
    ..The mechanisms that control the spatial organization of replication origins have potential impacts for genome regulation beyond replication. ..
  24. Woodfine K, Beare D, Ichimura K, Debernardi S, Mungall A, Fiegler H, et al. Replication timing of human chromosome 6. Cell Cycle. 2005;4:172-6 pubmed
    Genomic microarrays have been used to assess DNA replication timing in a variety of eukaryotic organisms. A replication timing map of the human genome has already been published at a 1Mb resolution...
  25. Shechter D, Costanzo V, Gautier J. ATR and ATM regulate the timing of DNA replication origin firing. Nat Cell Biol. 2004;6:648-55 pubmed
  26. D Antoni S, Mattina T, Di Mare P, Federico C, Motta S, Saccone S. Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and Velocardiofacial syndromes. Gene. 2004;333:111-9 pubmed
    ..We propose that the alteration in the replication/nuclear location pattern of the non-deleted TDR22 indicates an altered gene regulation hence an altered transcritpion in DGS/VCFS. ..
  27. Ryba T, Battaglia D, Chang B, Shirley J, Buckley Q, Pope B, et al. Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia. Genome Res. 2012;22:1833-44 pubmed publisher
    ..They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers. ..
  28. Oda M, Kanoh Y, Watanabe Y, Masai H. Regulation of DNA replication timing on human chromosome by a cell-type specific DNA binding protein SATB1. PLoS ONE. 2012;7:e42375 pubmed publisher
    ..Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome. ..
  29. Woo Y, Li W. DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes. Nat Commun. 2012;3:1004 pubmed publisher
    ..These observations show that replication timing has a prominent role in shaping the single-nucleotide variation landscape of cancer cells. ..
  30. Koren A, Polak P, Nemesh J, Michaelson J, Sebat J, Sunyaev S, et al. Differential relationship of DNA replication timing to different forms of human mutation and variation. Am J Hum Genet. 2012;91:1033-40 pubmed publisher
    ..To enable deeper investigation of how DNA replication timing relates to human mutation and variation, we generated a high-resolution map of the human genome's ..
  31. Retkute R, Nieduszynski C, de Moura A. Dynamics of DNA replication in yeast. Phys Rev Lett. 2011;107:068103 pubmed
    ..Our results compare favorably with experimental measurements in Saccharomyces cerevisae. ..
  32. Pink C, Hurst L. Timing of replication is a determinant of neutral substitution rates but does not explain slow Y chromosome evolution in rodents. Mol Biol Evol. 2010;27:1077-86 pubmed publisher
    ..These results support the hypothesis that replication timing is an important source of substitution rate heterogeneity...
  33. Hayashi M, Takahashi T, Nakagawa T, Nakayama J, Masukata H. The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus. Nat Cell Biol. 2009;11:357-62 pubmed publisher
    ..Our results show that a heterochromatic protein positively regulates initiation of replication in silenced chromatin by interacting with an essential kinase. ..
  34. Wu R, Singh P, Gilbert D. Uncoupling global and fine-tuning replication timing determinants for mouse pericentric heterochromatin. J Cell Biol. 2006;174:185-94 pubmed
  35. Eshaghi M, Karuturi R, Li J, Chu Z, Liu E, Liu J. Global profiling of DNA replication timing and efficiency reveals that efficient replication/firing occurs late during S-phase in S. pombe. PLoS ONE. 2007;2:e722 pubmed
    ..Current studies of genome-wide DNA replication profiles have focused on the DNA replication timing and origin location...
  36. Reyes Lamothe R, Possoz C, Danilova O, Sherratt D. Independent positioning and action of Escherichia coli replisomes in live cells. Cell. 2008;133:90-102 pubmed publisher
    ..We conclude that independent replication forks follow the path of the compacted chromosomal DNA, with no structure other than DNA anchoring the replisome to any particular cellular region...
  37. Goren A, Tabib A, Hecht M, Cedar H. DNA replication timing of the human beta-globin domain is controlled by histone modification at the origin. Genes Dev. 2008;22:1319-24 pubmed publisher
    ..In contrast, tethering of a histone deacetylase in erythroblasts causes a shift to late replication. These results suggest that histone modification at the origin serves as a binary switch for controlling replication timing. ..
  38. Farkash Amar S, Lipson D, Polten A, Goren A, Helmstetter C, Yakhini Z, et al. Global organization of replication time zones of the mouse genome. Genome Res. 2008;18:1562-70 pubmed publisher
    ..These findings, along with the strong conservation found between replication timing in human and mouse genomes, emphasize the importance of replication timing in transcription regulation. ..
  39. Yaffe E, Farkash Amar S, Polten A, Yakhini Z, Tanay A, Simon I. Comparative analysis of DNA replication timing reveals conserved large-scale chromosomal architecture. PLoS Genet. 2010;6:e1001011 pubmed publisher
    ..These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome. ..
  40. Ma E, Hyrien O, Goldar A. Do replication forks control late origin firing in Saccharomyces cerevisiae?. Nucleic Acids Res. 2012;40:2010-9 pubmed publisher
    Recent studies of eukaryotic DNA replication timing profiles suggest that the time-dependent rate of origin firing, I(t), has a universal shape, which ensures a reproducible replication completion time...
  41. Kohn K, Aladjem M, Weinstein J, Pommier Y. Chromatin challenges during DNA replication: a systems representation. Mol Biol Cell. 2008;19:1-7 pubmed
    ..on the complexities of chromatin replication, thereby providing a tool for system-level comprehension of the effects of genetic mutations, altered gene expression, and pharmacologic intervention. ..
  42. Thayer M. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes. Bioessays. 2012;34:760-70 pubmed publisher
  43. Bénard M, Maric C, Pierron G. Low rate of replication fork progression lengthens the replication timing of a locus containing an early firing origin. Nucleic Acids Res. 2007;35:5763-74 pubmed
    ..Importantly, we evidenced that the origin linked to php gene in plasmodium is not fired in amoebae when php expression dramatically reduced, further illustrating replication-transcription coupling in Physarum. ..
  44. Okamoto A, Utani K, Shimizu N. DNA replication occurs in all lamina positive micronuclei, but never in lamina negative micronuclei. Mutagenesis. 2012;27:323-7 pubmed publisher
    ..Taken together, these findings uncovered the DNA replication occurring inside micronuclei. ..
  45. Magner D, Blankschien M, Lee J, Pennington J, Lupski J, Rosenberg S. RecQ promotes toxic recombination in cells lacking recombination intermediate-removal proteins. Mol Cell. 2007;26:273-86 pubmed
    ..The data imply that RecQ promotes the net accumulation of BRIs in vivo, indicating a second paradigm for the in vivo effect of RecQ-like proteins. The E. coli RecQ paradigm may provide a useful model for some human RecQ homologs. ..
  46. van der Aa N, Cheng J, Mateiu L, Zamani Esteki M, Kumar P, Dimitriadou E, et al. Genome-wide copy number profiling of single cells in S-phase reveals DNA-replication domains. Nucleic Acids Res. 2013;41:e66 pubmed publisher
  47. Cohen S, Furey T, Doggett N, Kaufman D. Genome-wide sequence and functional analysis of early replicating DNA in normal human fibroblasts. BMC Genomics. 2006;7:301 pubmed
    ..These data suggest that there is a temporal pattern of replication for some functionally related genes. ..
  48. Schluth C, Cossee M, Girard Lemaire F, Carelle N, Dollfus H, Jeandidier E, et al. Phenotype in X chromosome rearrangements: pitfalls of X inactivation study. Pathol Biol (Paris). 2007;55:29-36 pubmed
    ..In this context, the prognostic value of X inactivation study in prenatal diagnosis will be discussed. ..
  49. Jiang H, Sha S, Schacht J. NF-kappaB pathway protects cochlear hair cells from aminoglycoside-induced ototoxicity. J Neurosci Res. 2005;79:644-51 pubmed
    ..These results suggest that changes in the redox state of the cochlea stimulate the activation of NF-kappaB and that this activation is cell protective. ..
  50. Lechel A, Manns M, Rudolph K. Telomeres and telomerase: new targets for the treatment of liver cirrhosis and hepatocellular carcinoma. J Hepatol. 2004;41:491-7 pubmed
  51. Seo J, Kim K, Chang D, Kang H, Shin E, Kwon J, et al. Genome-wide reorganization of histone H2AX toward particular fragile sites on cell activation. Nucleic Acids Res. 2014;42:1016-25 pubmed publisher
    ..Our findings suggest that active DNA replication is accompanied with the specific localization of H2AX and INO80 for efficient damage repair or replication-fork stabilization in actively transcribed regions. ..
  52. Shi K, Huang W, Aihara H. An enzyme-catalyzed multistep DNA refolding mechanism in hairpin telomere formation. PLoS Biol. 2013;11:e1001472 pubmed publisher
    ..The enzyme-catalyzed, multistep strand refolding is a novel mechanism in DNA rearrangement reactions. ..
  53. Parajuli S, Teasley D, Murali B, Jackson J, Vindigni A, Stewart S. Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork. J Biol Chem. 2017;292:15216-15224 pubmed publisher