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Up and Down the Slope: Replication Timing and Fork Directionality Gradients in Eukaryotic Genomes

  • Olivier Hyrien
Chapter

Abstract

Modern techniques allow the genome-wide determination of the replication time (RT) of any sequence in eukaryotic cell populations. Because origin firing is stochastic, the mean replication time (MRT) of a locus in a cell population depends on the firing time probability distribution of both neighboring and distant origins as well as on replication fork progression rates. Interpreting MRT profiles in terms of origin firing is therefore delicate. Theory predicts a simple relationship between the derivative (slope) of MRT profiles, the speed of replication forks, and the proportions of rightward- and leftward-moving forks replicating that locus (replication fork directionality; RFD). RFD profiles have been obtained by several independent methods: derivative of MRT profiles; nucleotide compositional skew analysis; sequencing of purified Okazaki fragments; and analysis of biased ribonucleotide incorporation in the two strands of the DNA. Using mathematical models, both MRT and RFD profiles allow quantitative inferences about the location and timing of replication initiation and termination events genome-wide. We summarize results and models of the replication program obtained by these approaches and their potential links with replication foci, chromatin states, and globular chromosomal domains.

Keywords

Replication origins Replication termini Replication fork Chromatin structure Mathematical modelling 

References

  1. 1.
    Hyrien O. Peaks cloaked in the mist: the landscape of mammalian replication origins. J Cell Biol. 2015;208(2):147–60.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Hyrien O, Rappailles A, Guilbaud G, Baker A, Chen CL, Goldar A, et al. From simple bacterial and archaeal replicons to replication n/u-domains. J Mol Biol. 2013;425(23):4673–89.PubMedCrossRefGoogle Scholar
  3. 3.
    Berezney R, Dubey DD, Huberman JA. Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci. Chromosoma. 2000;108(8):471–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Bechhoefer J, Rhind N. Replication timing and its emergence from stochastic processes. Trends Genet. 2012;28:374–81.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Rhind N, Gilbert DM. DNA replication timing. Cold Spring Harbor Perspect Med. 2013;3(7):1–26.Google Scholar
  6. 6.
    Fangman WL, Brewer BJ. Activation of replication origins within yeast chromosomes. Annu Rev Cell Biol. 1991;7:375–402.PubMedCrossRefGoogle Scholar
  7. 7.
    Tognetti S, Riera A, Speck C. Switch on the engine: how the eukaryotic replicative helicase MCM2-7 becomes activated. Chromosoma. 2014.Google Scholar
  8. 8.
    Raghuraman MK, Brewer BJ. Molecular analysis of the replication program in unicellular model organisms. Chromosome Res. 2010;18(1):19–34.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Newlon CS, Theis JF. The structure and function of yeast ARS elements. Curr Opin Genet Dev. 1993;3(5):752–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Czajkowsky DM, Liu J, Hamlin JL, Shao Z. DNA combing reveals intrinsic temporal disorder in the replication of yeast chromosome VI. J Mol Biol. 2008;375(1):12–9.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Bell SP, Stillman B. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex [see comments]. Nature. 1992;357(6374):128–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Gilbert DM. Evaluating genome-scale approaches to eukaryotic DNA replication. Nat Rev Genet. 2010;11(10):673–84.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Pope BD, Gilbert DM. The replication domain model: regulating replicon firing in the context of large-scale chromosome architecture. J Mol Biol. 2013;425(23):4690–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Guilbaud G, Rappailles A, Baker A, Chen CL, Arneodo A, Goldar A, et al. Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome. PLoS Comput Biol. 2011;7(12):e1002322.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Hiratani I, Ryba T, Itoh M, Yokochi T, Schwaiger M, Chang CW, et al. Global reorganization of replication domains during embryonic stem cell differentiation. PLoS Biol. 2008;6(10), e245.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Huberman JA, Riggs AD. On the mechanism of DNA replication in mammalian chromosomes. J Mol Biol. 1968;32(2):327–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Yurov YB, Liapunova NA. The units of DNA replication in the mammalian chromosomes: evidence for a large size of replication units. Chromosoma. 1977;60(3):253–67.PubMedCrossRefGoogle Scholar
  18. 18.
    Lebofsky R, Heilig R, Sonnleitner M, Weissenbach J, Bensimon A. DNA replication origin interference increases the spacing between initiation events in human cells. Mol Biol Cell. 2006;17(12):5337–45.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Norio P, Kosiyatrakul S, Yang Q, Guan Z, Brown NM, Thomas S, et al. Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development. Mol Cell. 2005;20(4):575–87.PubMedCrossRefGoogle Scholar
  20. 20.
    Demczuk A, Gauthier MG, Veras I, Kosiyatrakul S, Schildkraut CL, Busslinger M, et al. Regulation of DNA replication within the immunoglobulin heavy-chain locus during B cell commitment. PLoS Biol. 2012;10(7), e1001360.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Letessier A, Millot GA, Koundrioukoff S, Lachages AM, Vogt N, Hansen RS, et al. Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature. 2011;470(7332):120–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Yurov YB. Rate of DNA replication fork movement within a single mammalian cell. J Mol Biol. 1980;136(3):339–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Anglana M, Apiou F, Bensimon A, Debatisse M. Dynamics of DNA replication in mammalian somatic cells: nucleotide pool modulates origin choice and interorigin spacing. Cell. 2003;114(3):385–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Takebayashi S, Sugimura K, Saito T, Sato C, Fukushima Y, Taguchi H, et al. Regulation of replication at the R/G chromosomal band boundary and pericentromeric heterochromatin of mammalian cells. Exp Cell Res. 2005;304(1):162–74.PubMedCrossRefGoogle Scholar
  25. 25.
    Housman D, Huberman JA. Changes in the rate of DNA replication fork movement during S phase in mammalian cells. J Mol Biol. 1975;94(2):173–81.PubMedCrossRefGoogle Scholar
  26. 26.
    Goldar A, Marsolier-Kergoat MC, Hyrien O. Universal temporal profile of replication origin activation in eukaryotes. PLoS One. 2009;4(6), e5899.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Lucas I, Chevrier-Miller M, Sogo JM, Hyrien O. Mechanisms ensuring rapid and complete DNA replication despite random initiation in Xenopus early embryos. J Mol Biol. 2000;296(3):769–86.PubMedCrossRefGoogle Scholar
  28. 28.
    Herrick J, Jun S, Bechhoefer J, Bensimon A. Kinetic model of DNA replication in eukaryotic organisms. J Mol Biol. 2002;320(4):741–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Yang SC, Rhind N, Bechhoefer J. Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing. Mol Syst Biol. 2010;6:404.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Goldar A, Labit H, Marheineke K, Hyrien O. A dynamic stochastic model for DNA replication initiation in early embryos. PLoS One. 2008;3(8), e2919.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Gauthier MG, Bechhoefer J. Control of DNA replication by anomalous reaction-diffusion kinetics. Phys Rev Lett. 2009;102(15):158104.PubMedCrossRefGoogle Scholar
  32. 32.
    Ma E, Hyrien O, Goldar A. Do replication forks control late origin firing in Saccharomyces cerevisiae? Nucleic Acids Res. 2012;40(5):2010–9.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Raghuraman MK, Winzeler EA, Collingwood D, Hunt S, Wodicka L, Conway A, et al. Replication dynamics of the yeast genome. Science. 2001;294(5540):115–21.PubMedCrossRefGoogle Scholar
  34. 34.
    Friedman KL, Brewer BJ, Fangman WL. Replication profile of Saccharomyces cerevisiae chromosome VI. Genes Cells. 1997;2(11):667–78.PubMedCrossRefGoogle Scholar
  35. 35.
    Yamashita M, Hori Y, Shinomiya T, Obuse C, Tsurimoto T, Yoshikawa H, et al. The efficiency and timing of initiation of replication of multiple replicons of Saccharomyces cerevisiae chromosome VI. Genes Cells. 1997;2(11):655–65.PubMedCrossRefGoogle Scholar
  36. 36.
    de Moura AP, Retkute R, Hawkins M, Nieduszynski CA. Mathematical modelling of whole chromosome replication. Nucleic Acids Res. 2010;38:5623–63.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Retkute R, Nieduszynski CA, de Moura A. Dynamics of DNA replication in yeast. Phys Rev Lett. 2011;107(6):068103.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Retkute R, Nieduszynski CA, de Moura A. Mathematical modeling of genome replication. Phys Rev E Stat Nonlin Soft Matter Phys. 2012;86(3 Pt 1):031916.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Baker A, Audit B, Chen C-L, Moindrot B, Leleu A, Guilbaud G, et al. Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines. PLoS Comput Biol. 2012;8(4), e1002443.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    McGuffee SR, Smith DJ, Whitehouse I. Quantitative, genome-wide analysis of eukaryotic replication initiation and termination. Mol Cell. 2013;50(1):123–35.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Audit B, Baker A, Chen CL, Rappailles A, Guilbaud G, Julienne H, et al. Multiscale analysis of genome-wide replication timing profiles using a wavelet-based signal-processing algorithm. Nat Protoc. 2013;8(1):98–110.PubMedCrossRefGoogle Scholar
  42. 42.
    Baker A, Bechhoefer J. Inferring the spatiotemporal DNA replication program from noisy data. Phys Rev E Stat Nonlin Soft Matter Phys. 2014;89(3):032703.PubMedCrossRefGoogle Scholar
  43. 43.
    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(12):2288–99.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Muller CA, Hawkins M, Retkute R, Malla S, Wilson R, Blythe MJ, et al. The dynamics of genome replication using deep sequencing. Nucleic Acids Res. 2014;42(1), e3.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Koren A, Handsaker RE, Kamitaki N, Karli R, Ghosh S, Polak P, et al. Genetic variation in human DNA replication timing. Cell. 2014;159(5):1015–26.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Sekedat MD, Fenyo D, Rogers RS, Tackett AJ, Aitchison JD, Chait BT. GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome. Mol Syst Biol. 2010;6:353.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Feng W, Collingwood D, Boeck ME, Fox LA, Alvino GM, Fangman WL, et al. Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nat Cell Biol. 2006;8(2):148–55.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Hawkins M, Retkute R, Muller CA, Saner N, Tanaka TU, de Moura AP, et al. High-resolution replication profiles define the stochastic nature of genome replication initiation and termination. Cell Rep. 2013;5(4):1132–41.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Chen CL, 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.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Hansen RS, Thomas S, Sandstrom R, Canfield TK, Thurman RE, Weaver M, et al. Sequencing newly replicated DNA reveals widespread plasticity in human replication timing. Proc Natl Acad Sci U S A. 2010;107(1):139–44.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Lobry JR. Asymmetric substitution patterns in the two DNA strands of bacteria. Mol Biol Evol. 1996;13(5):660–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Touchon M, Nicolay S, Audit B, Brodie Of Brodie EB, d'Aubenton-Carafa Y, Arneodo A, et al. Replication-associated strand asymmetries in mammalian genomes: toward detection of replication origins. Proc Natl Acad Sci U S A. 2005;28:28.Google Scholar
  53. 53.
    Brodie Of Brodie EB, Nicolay S, Touchon EB, Audit B, d'Aubenton-Carafa Y, Thermes C, et al. From DNA sequence analysis to modeling replication in the human genome. Phys Rev Lett. 2005;94(24):248103.PubMedCrossRefGoogle Scholar
  54. 54.
    Huvet M, Nicolay S, Touchon M, Audit B, d'Aubenton-Carafa Y, Arneodo A, et al. Human gene organization driven by the coordination of replication and transcription. Genome Res. 2007;17(9):1278–85.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Chen CL, Duquenne L, Audit B, Guilbaud G, Rappailles A, Baker A, et al. Replication-associated mutational asymmetry in the human genome. Mol Biol Evol. 2011;28(8):2327–37.PubMedCrossRefGoogle Scholar
  56. 56.
    Necsulea A, Guillet C, Cadoret JC, Prioleau MN, Duret L. The relationship between DNA replication and human genome organization. Mol Biol Evol. 2009;26(4):729–41.PubMedCrossRefGoogle Scholar
  57. 57.
    Baker A, Nicolay S, Zaghloul L, d'Aubenton-Carafa Y, Thermes A, d'Aubenton-Carafa Y, Audit B, et al. Wavelet-based method to disentangle transcription- and replication-associated strand asymmetries in mammalian genomes. Appl Comput Harmon Anal. 2010;28:150–70.CrossRefGoogle Scholar
  58. 58.
    Marsolier-Kergoat MC, Goldar A. DNA replication induces compositional biases in yeast. Mol Biol Evol. 2012;29(3):893–904.PubMedCrossRefGoogle Scholar
  59. 59.
    Agier N, Fischer G. The mutational profile of the yeast genome is shaped by replication. Mol Biol Evol. 2012;29(3):905–13.PubMedCrossRefGoogle Scholar
  60. 60.
    Agier N, Romano OM, Touzain F, Cosentino Lagomarsino M, Fischer G. The spatiotemporal program of replication in the genome of Lachancea kluyveri. Genome Biol Evol. 2013;5(2):370–88.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Nick McElhinny SA, Kumar D, Clark AB, Watt DL, Watts BE, Lundstrom EB, et al. Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol. 2010;6(10):774–81.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Sparks JL, Chon H, Cerritelli SM, Kunkel TA, Johansson E, Crouch RJ, et al. RNase H2-initiated ribonucleotide excision repair. Mol Cell. 2012;47(6):980–6.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Miyabe I, Kunkel TA, Carr AM. The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet. 2011;7(12), e1002407.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Reijns MA, Kemp H, Ding J, de Proce SM, Jackson AP, Taylor MS. Lagging-strand replication shapes the mutational landscape of the genome. Nature. 2015;518(7540):502–6.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Daigaku Y, Keszthelyi A, Muller CA, Miyabe I, Brooks T, Retkute R, et al. A global profile of replicative polymerase usage. Nat Struct Mol Biol. 2015;22(3):192–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Clausen AR, Lujan SA. Tracking replication enzymology in vivo by genome-wide mapping of ribonucleotide incorporation. Nat Struct Mol Biol. 2015;22(3):185–91.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Koh KD, Balachander S, Hesselberth JR, Storici F. Ribose-seq: global mapping of ribonucleotides embedded in genomic DNA. Nat Methods. 2015;12(3):251–7.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Pursell ZF, Isoz I, Lundstrom EB, Johansson E, Kunkel TA. Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science. 2007;317(5834):127–30.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Nick McElhinny SA, Gordenin DA, Stith CM, Burgers PM, Kunkel TA. Division of labor at the eukaryotic replication fork. Mol Cell. 2008;30(2):137–44.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Lujan SA, Clausen AR, Clark AB, MacAlpine HK, MacAlpine DM, Malc EP, et al. Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition. Genome Res. 2014;24(11):1751–64.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Johnson RE, Classen R, Prakash L, Prakash S. A major role of DNA polymerase delta in replication of both the leading and lagging DNA strands. Mol. Cell 2015; 59(2):163-175.Google Scholar
  72. 72.
    Smith DJ, Whitehouse I. Intrinsic coupling of lagging-strand synthesis to chromatin assembly. Nature. 2012;483(7390):434–8.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Hyrien O, Goldar A. Mathematical modelling of eukaryotic DNA replication. Chromosome Res. 2010;18(1):147–61.PubMedCrossRefGoogle Scholar
  74. 74.
    Gauthier MG, Norio P, Bechhoefer J. Modeling inhomogeneous DNA replication kinetics. PLoS One. 2012;7(3), e32053.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Yang SC, Bechhoefer J. How Xenopus laevis embryos replicate reliably: investigating the random-completion problem. Phys Rev E Stat Nonlin Soft Matter Phys. 2008;78(4 Pt 1):041917.PubMedCrossRefGoogle Scholar
  76. 76.
    Kolmogorov AN. On the statistical theory of crystallization in metals. Izv Akad Nauk SSSR Ser Fiz. 1937;1:355–9.Google Scholar
  77. 77.
    Johnson WA, Mehl PA. Reaction kinetics in processes of nucleation and growth. Trans AIMME. 1939;135:416–42.Google Scholar
  78. 78.
    Avrami M. Kinetics of phase change. I. General theory. J Chem Phys. 1939;7:1103–12.CrossRefGoogle Scholar
  79. 79.
    Avrami M. Kinetics of phase change. II. Transformation-time relations for random distributions of nuclei. J Chem Phys. 1940;8:212–24.CrossRefGoogle Scholar
  80. 80.
    Avrami M. Kinetics of phase change. III. Granulation, phase change, and microstructure. J Chem Phys. 1941;9:177–84.CrossRefGoogle Scholar
  81. 81.
    Baker A, Audit B, Yang SC-H, Bechhoefer J, Arneodo A. Inferring where and when replication initiates from genome-wide replication timing data. Phys Rev Lett. 2012;108:268101.PubMedCrossRefGoogle Scholar
  82. 82.
    Patel PK, Kommajosyula N, Rosebrock A, Bensimon A, Leatherwood J, Bechhoefer J, et al. The Hsk1/Cdc7 replication kinase regulates origin efficiency. Mol Biol Cell. 2008;12:5550–8.CrossRefGoogle Scholar
  83. 83.
    Wu PY, Nurse P. Establishing the program of origin firing during S phase in fission Yeast. Cell. 2009;136(5):852–64.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    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(23):4805–14.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21(24):2055–63.PubMedCrossRefGoogle Scholar
  86. 86.
    Wong PG, Winter SL, Zaika E, Cao TV, Oguz U, Koomen JM, et al. Cdc45 limits replicon usage from a low density of preRCs in mammalian cells. PLoS One. 2011;6(3), e17533.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Wyrick JJ, Aparicio JG, Chen T, Barnett JD, Jennings EG, Young RA, et al. Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins. Science. 2001;294(5550):2357–60.PubMedCrossRefGoogle Scholar
  88. 88.
    Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009;139(4):719–30.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Bowers JL, Randell JC, Chen S, Bell SP. ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Mol Cell. 2004;16(6):967–78.PubMedCrossRefGoogle Scholar
  90. 90.
    Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, et al. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009;106(48):20240–5.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Belsky JA, MacAlpine HK, Lubelsky Y, Hartemink AJ, MacAlpine DM. Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly. Genes Dev. 2015;29(2):212–24.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Fachinetti D, Bermejo R, Cocito A, Minardi S, Katou Y, Kanoh Y, et al. Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements. Mol Cell. 2010;39(4):595–605.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Mukhopadhyay R, Lajugie J, Fourel N, Selzer A, Schizas M, Bartholdy B, et al. Allele-specific genome-wide profiling in human primary erythroblasts reveal replication program organization. PLoS Genet. 2014;10(5), e1004319.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Ryba T, Hiratani I, Lu J, Itoh M, Kulik M, Zhang J, et al. Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types. Genome Res. 2010;20(6):761–70.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Zaghloul L, Drillon G, Boulos RE, Argoul F, Thermes C, Arneodo A, et al. Large replication skew domains delimit GC-poor gene deserts in human. Comput Biol Chem. 2014;53 Pt A:153–65.PubMedCrossRefGoogle Scholar
  96. 96.
    Lima-de-Faria A, Jaworska H. Late DNA synthesis in heterochromatin. Nature. 1968;217(5124):138–42.PubMedCrossRefGoogle Scholar
  97. 97.
    Dimitrova DS, Gilbert DM. The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Mol Cell. 1999;4(6):983–93.PubMedCrossRefGoogle Scholar
  98. 98.
    O'Keefe RT, Henderson SC, Spector DL. Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J Cell Biol. 1992;116(5):1095–110.PubMedCrossRefGoogle Scholar
  99. 99.
    Sporbert A, Gahl A, Ankerhold R, Leonhardt H, Cardoso MC. DNA polymerase clamp shows little turnover at established replication sites but sequential de novo assembly at adjacent origin clusters. Mol Cell. 2002;10(6):1355–65.PubMedCrossRefGoogle Scholar
  100. 100.
    Maya-Mendoza A, Olivares-Chauvet P, Shaw A, Jackson DA. S phase progression in human cells is dictated by the genetic continuity of DNA foci. PLoS Genet. 2010;6(4), e1000900.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Audit B, Zaghloul L, Vaillant C, Chevereau G, d'Aubenton-Carafa Y, Thermes C, et al. Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells. Nucleic Acids Res. 2009;37(18):6064–75.PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Julienne H, Zoufir A, Audit B, Arneodo A. Human genome replication proceeds through four chromatin states. PLoS Comput Biol. 2013;9(10), e1003233.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289–93.PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485(7398):376–80.PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, Mirny LA, et al. Organization of the mitotic chromosome. Science. 2013;342(6161):948–53.PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Pope BD, Ryba T, Dileep V, Yue F, Wu W, Denas O, et al. Topologically associating domains are stable units of replication-timing regulation. Nature. 2014;515(7527):402–5.PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Gindin Y, Valenzuela MS, Aladjem MI, Meltzer PS, Bilke S. A chromatin structure-based model accurately predicts DNA replication timing in human cells. Mol Syst Biol. 2014;10:722.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Institut de Biologie de l’Ecole Normale Superieure (IBENS)CNRS UMR8197, Inserm U1024ParisFrance

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