Skip to main content

Regulation of Replication Origins

  • Chapter
  • First Online:
DNA Replication

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1042))

Abstract

In eukaryotes, genome duplication starts concomitantly at many replication initiation sites termed replication origins. The replication initiation program is spatially and temporally coordinated to ensure accurate, efficient DNA synthesis that duplicates the entire genome while maintaining other chromatin-dependent functions. Unlike in prokaryotes, not all potential replication origins in eukaryotes are needed for complete genome duplication during each cell cycle. Instead, eukaryotic cells vary the use of initiation sites so that only a fraction of potential replication origins initiate replication each cell cycle. Flexibility in origin choice allows each eukaryotic cell type to utilize different initiation sites, corresponding to unique nuclear DNA packaging patterns. These patterns coordinate replication with gene expression and chromatin condensation. Budding yeast replication origins share a consensus sequence that marks potential initiation sites. Metazoan origins, on the other hand, lack a consensus sequence. Rather, they are associated with a collection of structural features, chromatin packaging features, histone modifications, transcription, and DNA-DNA/DNA-protein interactions. These features confer cell type-specific replication and expression and play an essential role in maintaining genomic stability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Abbas T, Keaton MA, Dutta A (2013) Genomic instability in cancer. Cold Spring Harb Perspect Biol 5:a012914

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Abid A, Costa A (2016) The MCM helicase motor of the eukaryotic replisome. J Mol Biol 428:10

    Article  CAS  Google Scholar 

  • Aladjem MI (2007) Replication in context: dynamic regulation of DNA replication patterns in metazoans. Nat Rev Genet 8:588–600

    Article  CAS  PubMed  Google Scholar 

  • Aladjem MI, Rodewald LW, Kolman JL, Wahl GM (1998) Genetic dissection of a mammalian replicator in the human beta-globin locus. Science 281:1005–1009

    Article  CAS  PubMed  Google Scholar 

  • Anglana M, Apiou F, Bensimon A, Debatisse M (2003) Dynamics of DNA replication in mammalian somatic cells: nucleotide pool modulates origin choice and interorigin spacing. Cell 114:385–394

    Article  CAS  PubMed  Google Scholar 

  • Bartholdy B, Mukhopadhyay R, Lajugie J, Aladjem MI, Bouhassira EE (2015) Allele-specific analysis of DNA replication origins in mammalian cells. Nat Commun 6:7051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bar-Ziv R, Voichek Y, Barkai N (2016) Chromatin dynamics during DNA replication. Genome Res 26:1245–1256. https://doi.org/10.1101/gr.201244.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bell SP (2002) The origin recognition complex: from simple origins to complex functions. Genes Dev 16:659–672

    Article  CAS  PubMed  Google Scholar 

  • Besnard E, Babled A, Lapasset L, Milhavet O, Parrinello H, Dantec C, Marin JM, Lemaitre JM (2012) Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs. Nat Struct Mol Biol 19:837–844

    Article  CAS  PubMed  Google Scholar 

  • Blow JJ, Ge XQ, Jackson DA (2011) How dormant origins promote complete genome replication. Trends Biochem Sci 36:405–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boos D, Yekezare M, Diffley JF (2013) Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science 340:981–984

    Article  CAS  PubMed  Google Scholar 

  • Bruck I, Perez-Arnaiz P, Colbert MK, Kaplan DL (2015) Insights into the initiation of eukaryotic DNA replication. Nucleus 6:449–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bustin M, Misteli T (2016) Nongenetic functions of the genome. Science 352:aad6933

    Article  PubMed  CAS  Google Scholar 

  • Cayrou C, Coulombe P, Vigneron A, Stanojcic S, Ganier O, Peiffer I, Rivals E, Puy A, Laurent-Chabalier S, Desprat R et al (2011) Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features. Genome Res 21:1438–1449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cayrou C, Ballester B, Peiffer I, Fenouil R, Coulombe P, Andrau JC, van Helden J, Mechali M (2015) The chromatin environment shapes DNA replication origin organization and defines origin classes. Genome Res 25:1873–1885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chakraborty A, Shen Z, Prasanth SG (2011) “ORCanization” on heterochromatin: linking DNA replication initiation to chromatin organization. Epigenetics 6:665–670

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Liu G, Leffak M (2013) Activation of a human chromosomal replication origin by protein tethering. Nucleic Acids Res 41:6460–6474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conner AL, Aladjem MI (2012) The chromatin backdrop of DNA replication: lessons from genetics and genome-scale analyses. Biochim Biophys Acta 1819:794–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conti C, Leo E, Eichler GS, Sordet O, Martin MM, Fan A, Aladjem MI, Pommier Y (2010) Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res 70:4470–4480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornacchia D, Dileep V, Quivy JP, Foti R, Tili F, Santarella-Mellwig R, Antony C, Almouzni G, Gilbert DM, Buonomo SB (2012) Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells. EMBO J 31:3678–3690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daboussi F, Courbet S, Benhamou S, Kannouche P, Zdzienicka MZ, Debatisse M, Lopez BS (2008) A homologous recombination defect affects replication-fork progression in mammalian cells. J Cell Sci 121:162–166

    Article  CAS  PubMed  Google Scholar 

  • Das SP, Borrman T, Liu VW, Yang SC, Bechhoefer J, Rhind N (2015) Replication timing is regulated by the number of MCMs loaded at origins. Genome Res 25:1886–1892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dave A, Cooley C, Garg M, Bianchi A (2014) Protein phosphatase 1 recruitment by Rif1 regulates DNA replication origin firing by counteracting DDK activity. Cell Rep 7:53–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DePamphilis ML (1999) Replication origins in metazoan chromosomes: fact or fiction? BioEssays 21:5–16

    Article  CAS  PubMed  Google Scholar 

  • Depamphilis ML, de Renty CM, Ullah Z, Lee CY (2012) “The Octet”: eight protein kinases that control mammalian DNA replication. Front Physiol 3:368

    Article  PubMed  PubMed Central  Google Scholar 

  • Dershowitz A, Snyder M, Sbia M, Skurnick JH, Ong LY, Newlon CS (2007) Linear derivatives of Saccharomyces cerevisiae chromosome III can be maintained in the absence of autonomously replicating sequence elements. Mol Cell Biol 27:4652–4663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dileep V, Ay F, Sima J, Vera DL, Noble WS, Gilbert DM (2015) Topologically associating domains and their long-range contacts are established during early G1 coincident with the establishment of the replication-timing program. Genome Res 25:1104–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donley N, Smith L, Thayer MJ (2015) ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15. PLoS Genet 11:e1004923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fanning E, Zhao K (2009) SV40 DNA replication: from the A gene to a nanomachine. Virology 384:352–359

    Article  CAS  PubMed  Google Scholar 

  • Feng YQ, Desprat R, Fu H, Olivier E, Lin CM, Lobell A, Gowda SN, Aladjem MI, Bouhassira EE (2006) DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLoS Genet 2:e65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Flickinger RA (2015) Possible role of H1 histone in replication timing. Develop Growth Differ 57:1–9

    Article  CAS  Google Scholar 

  • Foti R, Gnan S, Cornacchia D, Dileep V, Bulut-Karslioglu A, Diehl S, Buness A, Klein FA, Huber W, Johnstone E et al (2016) Nuclear architecture organized by Rif1 underpins the replication-timing program. Mol Cell 61:260–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foulk MS, Urban JM, Casella C, Gerbi SA (2015) Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins. Genome Res 25:725–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fragkos M, Ganier O, Coulombe P, Mechali M (2015) DNA replication origin activation in space and time. Nat Rev Mol Cell Biol 16:360–374

    Article  CAS  PubMed  Google Scholar 

  • Francis LI, Randell JC, Takara TJ, Uchima L, Bell SP (2009) Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylation. Genes Dev 23:643–654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu H, Wang L, Lin CM, Singhania S, Bouhassira EE, Aladjem MI (2006) Preventing gene silencing with human replicators. Nat Biotechnol 24:572–576

    Article  CAS  PubMed  Google Scholar 

  • Fu H, Martin MM, Regairaz M, Huang L, You Y, Lin CM, Ryan M, Kim R, Shimura T, Pommier Y et al (2015) The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage. Nat Commun 6:6746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerhardt J, Tomishima MJ, Zaninovic N, Colak D, Yan Z, Zhan Q, Rosenwaks Z, Jaffrey SR, Schildkraut CL (2014) The DNA replication program is altered at the FMR1 locus in fragile X embryonic stem cells. Mol Cell 53:19–31

    Article  CAS  PubMed  Google Scholar 

  • Gindin Y, Valenzuela MS, Aladjem MI, Meltzer PS, Bilke S (2014) A chromatin structure-based model accurately predicts DNA replication timing in human cells. Mol Syst Biol 10:722

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Giri S, Aggarwal V, Pontis J, Shen Z, Chakraborty A, Khan A, Mizzen C, Prasanth KV, Ait-Si-Ali S, Ha T et al (2015). The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin. Elife 4

    Google Scholar 

  • Hanlon SL, Li JJ (2015) Re-replication of a centromere induces chromosomal instability and aneuploidy. PLoS Genet 11:e1005039

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hassan-Zadeh V, Chilaka S, Cadoret JC, Ma MK, Boggetto N, West AG, Prioleau MN (2012) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. PLoS Biol 10:e1001277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayano M, Kanoh Y, Matsumoto S, Renard-Guillet C, Shirahige K, Masai H (2012) Rif1 is a global regulator of timing of replication origin firing in fission yeast. Genes Dev 26:137–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiraga S, Alvino GM, Chang F, Lian HY, Sridhar A, Kubota T, Brewer BJ, Weinreich M, Raghuraman MK, Donaldson AD (2014) Rif1 controls DNA replication by directing protein phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. Genes Dev 28:372–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiratani I, Ryba T, Itoh M, Rathjen J, Kulik M, Papp B, Fussner E, Bazett-Jones DP, Plath K, Dalton S et al (2010) Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis. Genome Res 20:155–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoggard T, Shor E, Muller CA, Nieduszynski CA, Fox CA (2013) A link between ORC-origin binding mechanisms and origin activation time revealed in budding yeast. PLoS Genet 9:e1003798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang D, Koshland D (2003) Chromosome integrity in Saccharomyces cerevisiae: the interplay of DNA replication initiation factors, elongation factors, and origins. Genes Dev 17:1741–1754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM (2006) Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Science 312:748–751

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Fu H, Lin CM, Conner AL, Zhang Y, Aladjem MI (2011) Prevention of transcriptional silencing by a replicator-binding complex consisting of SWI/SNF, MeCP1, and hnRNP C1/C2. Mol Cell Biol 31:3472–3484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iizuka M, Matsui T, Takisawa H, Smith MM (2006) Regulation of replication licensing by acetyltransferase Hbo1. Mol Cell Biol 26:1098–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacob F, Brenner J, Cuzin F (1963) On the regulation of DNA replication in bacteria. Cold Spring Harbor Dymp Quant Biol 28:329

    Article  CAS  Google Scholar 

  • Kanemaki M, Labib K (2006) Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks. EMBO J 25:1753–1763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanoh Y, Matsumoto S, Fukatsu R, Kakusho N, Kono N, Renard-Guillet C, Masuda K, Iida K, Nagasawa K, Shirahige K et al (2015) Rif1 binds to G quadruplexes and suppresses replication over long distances. Nat Struct Mol Biol 22:889–897

    Article  CAS  PubMed  Google Scholar 

  • Kawabata T, Luebben SW, Yamaguchi S, Ilves I, Matise I, Buske T, Botchan MR, Shima N (2011) Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol Cell 41:543–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim J, Daniel J, Espejo A, Lake A, Krishna M, Xia L, Zhang Y, Bedford MT (2006) Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep 7:397–403

    CAS  PubMed  PubMed Central  Google Scholar 

  • Knott SR, Peace JM, Ostrow AZ, Gan Y, Rex AE, Viggiani CJ, Tavare S, Aparicio OM (2012) Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Cell 148:99–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koren A, Handsaker RE, Kamitaki N, Karlic R, Ghosh S, Polak P, Eggan K, McCarroll SA (2014) Genetic variation in human DNA replication timing. Cell 159:1015–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lengronne A, Schwob E (2002) The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G(1). Mol Cell 9:1067–1078

    Article  CAS  PubMed  Google Scholar 

  • Leonard AC, Mechali M (2013) DNA replication origins. Cold Spring Harb Perspect Biol 5:a010116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu G, Malott M, Leffak M (2003) Multiple functional elements comprise a mammalian chromosomal replicator. Mol Cell Biol 23:1832–1842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lob D, Lengert N, Chagin VO, Reinhart M, Casas-Delucchi CS, Cardoso MC, Drossel B (2016) 3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression. Nat Commun 7:11207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majocchi S, Aritonovska E, Mermod N (2014) Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes. Nucleic Acids Res 42:193–204

    Article  CAS  PubMed  Google Scholar 

  • Marahrens Y, Stillman B (1992) A yeast chromosomal origin of DNA replication defined by multiple functional elements. Science 255:817–823

    Article  CAS  PubMed  Google Scholar 

  • Marks AB, Smith OK, Aladjem MI (2016) Replication origins: determinants or consequences of nuclear organization? Curr Opin Genet Dev 37:67–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin MM, Ryan M, Kim R, Zakas AL, Fu H, Lin CM, Reinhold WC, Davis SR, Bilke S, Liu H et al (2011) Genome-wide depletion of replication initiation events in highly transcribed regions. Genome Res 21:1822–1832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M (2010) Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem 79:89–130

    Article  CAS  PubMed  Google Scholar 

  • Mattarocci S, Shyian M, Lemmens L, Damay P, Altintas DM, Shi T, Bartholomew CR, Thoma NH, Hardy CF, Shore D (2014) Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7. Cell Rep 7:62–69

    Article  CAS  PubMed  Google Scholar 

  • Mechali M, Kearsey S (1984) Lack of specific sequence requirement for DNA replication in Xenopus eggs compared with high sequence specificity in yeast. Cell 38:55–64

    Article  CAS  PubMed  Google Scholar 

  • Mechali M, Yoshida K, Coulombe P, Pasero P (2013) Genetic and epigenetic determinants of DNA replication origins, position and activation. Curr Opin Genet Dev 23:124–131

    Article  CAS  PubMed  Google Scholar 

  • Miotto B, Struhl K (2010) HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin. Mol Cell 37:57–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miotto B, Ji Z, Struhl K (2016) Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers. Proc Natl Acad Sci U S A 113:E4810-9

    Article  PubMed  CAS  Google Scholar 

  • Moindrot B, Audit B, Klous P, Baker A, Thermes C, de Laat W, Bouvet P, Mongelard F, Arneodo A (2012) 3D chromatin conformation correlates with replication timing and is conserved in resting cells. Nucleic Acids Res 40:9470–9481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukhopadhyay R, Lajugie J, Fourel N, Selzer A, Schizas M, Bartholdy B, Mar J, Lin CM, Martin MM, Ryan M et al (2014) Allele-specific genome-wide profiling in human primary erythroblasts reveal replication program organization. PLoS Genet 10:e1004319

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Musialek MW, Rybaczek D (2015) Behavior of replication origins in Eukaryota – spatio-temporal dynamics of licensing and firing. Cell Cycle 14:2251–2264

    Google Scholar 

  • Nagano T, Fraser P (2011) No-nonsense functions for long noncoding RNAs. Cell 145:178–181

    Article  CAS  PubMed  Google Scholar 

  • Norio P, Kosiyatrakul S, Yang Q, Guan Z, Brown NM, Thomas S, Riblet R, Schildkraut CL (2005) Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development. Mol Cell 20:575–587

    Article  CAS  PubMed  Google Scholar 

  • Palacios DeBeer MA, Muller U, Fox CA (2003) Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin. Genes Dev 17:1817–1822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peace JM, Villwock SK, Zeytounian JL, Gan Y, Aparicio OM (2016) Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and Fkh2 are rate-limiting activators of replication origins that reprogram replication timing in G1 phase. Genome Res 26:365–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pope BD, Ryba T, Dileep V, Yue F, Wu W, Denas O, Vera DL, Wang Y, Hansen RS, Canfield TK et al (2014) Topologically associating domains are stable units of replication-timing regulation. Nature 515:402–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES et al (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665–1680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Remus D, Diffley JF (2009) Eukaryotic DNA replication control: lock and load, then fire. Curr Opin Cell Biol 21:771–777

    Article  CAS  PubMed  Google Scholar 

  • Rhind N, Gilbert DM (2013a) DNA replication timing. Cold Spring Harb Perspect Med 3:1–26

    Google Scholar 

  • Rhind N, Gilbert DM (2013b) DNA replication timing. Cold Spring Harb Perspect Biol 5:a010132

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Richardson CD, Li JJ (2014) Regulatory mechanisms that prevent re-initiation of DNA replication can be locally modulated at origins by nearby sequence elements. PLoS Genet 10:e1004358

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rivera-Mulia JC, Gilbert DM (2016) Replication timing and transcriptional control: beyond cause and effect-part III. Curr Opin Cell Biol 40:168–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivera-Mulia JC, Buckley Q, Sasaki T, Zimmerman J, Didier RA, Nazor K, Loring JF, Lian Z, Weissman S, Robins AJ et al (2015) Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells. Genome Res 25:1091–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saksouk N, Avvakumov N, Champagne KS, Hung T, Doyon Y, Cayrou C, Paquet E, Ullah M, Landry AJ, Côté V et al (2009) HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail. Mol Cell 33:257–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sansam CG, Goins D, Siefert JC, Clowdus EA, Sansam CL (2015) Cyclin-dependent kinase regulates the length of S phase through TICRR/TRESLIN phosphorylation. Genes Dev 29:555–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwaiger M, Kohler H, Oakeley EJ, Stadler MB, Schubeler D (2010) Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome. Genome Res 20:771–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sequeira-Mendes J, Diaz-Uriarte R, Apedaile A, Huntley D, Brockdorff N, Gomez M (2009) Transcription initiation activity sets replication origin efficiency in mammalian cells. PLoS Genet 5:e1000446

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sherstyuk VV, Shevchenko AI, Zakian SM (2014) Epigenetic landscape for initiation of DNA replication. Chromosoma 123:183–199

    Article  CAS  PubMed  Google Scholar 

  • Sheu YJ, Kinney JB, Stillman B (2016) Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression. Genome Res 26:315–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith OK, Aladjem MI (2014) Chromatin structure and replication origins: determinants of chromosome replication and nuclear organization. J Mol Biol 426:3330–3341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith OK, Kim R, Fu H, Martin MM, Lin CM, Utani K, Zhang Y, Marks AB, Lalande M, Chamberlain S et al (2016) Distinct epigenetic features of differentiation-regulated replication origins. Epigenetics Chromatin 9:18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takayama Y, Kamimura Y, Okawa M, Muramatsu S, Sugino A, Araki H (2003) GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev 17:1153–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka S, Araki H (2013) Helicase activation and establishment of replication forks at chromosomal origins of replication. Cold Spring Harb Perspect Biol 5:a010371

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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. Nat Cell Biol 12:1086–1093

    Article  CAS  PubMed  Google Scholar 

  • Tazumi A, Fukuura M, Nakato R, Kishimoto A, Takenaka T, Ogawa S, Song JH, Takahashi TS, Nakagawa T, Shirahige K et al (2012) Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast. Genes Dev 26:2050–2062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuduri S, Crabbe L, Conti C, Tourriere H, Holtgreve-Grez H, Jauch A, Pantesco V, De Vos J, Thomas A, Theillet C et al (2009) Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol 11:1315–1324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urban JM, Foulk MS, Casella C, Gerbi SA (2015) The hunt for origins of DNA replication in multicellular eukaryotes. F1000prime Rep 7:30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Valenzuela MS, Chen Y, Davis S, Yang F, Walker RL, Bilke S, Lueders J, Martin MM, Aladjem MI, Massion PP et al (2011) Preferential localization of human origins of DNA replication at the 5′-ends of expressed genes and at evolutionarily conserved DNA sequences. Plos One 6:e17308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogelauer M, Rubbi L, Lucas I, Brewer BJ, Grunstein M (2002) Histone acetylation regulates the time of replication origin firing. Mol Cell 10:1223–1233

    Article  CAS  PubMed  Google Scholar 

  • Wu JR, Gilbert DM (1996) A distinct G1 step required to specify the Chinese hamster DHFR replication origin. Science 271:1270–1272

    Article  CAS  PubMed  Google Scholar 

  • Yaffe E, Farkash-Amar S, Polten A, Yakhini Z, Tanay A, Simon I (2010) Comparative analysis of DNA replication timing reveals conserved large-scale chromosomal architecture. PLoS Genet 6:e1001011

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamazaki S, Ishii A, Kanoh Y, Oda M, Nishito Y, Masai H (2012) Rif1 regulates the replication timing domains on the human genome. EMBO J 31:3667–3677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zegerman P, Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445:281–285

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Huang L, Fu H, Smith OK, Lin CM, Utani K, Rao M, Reinhold WC, Redon CE, Ryan M et al (2016) A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells. Nat Commun 7:11748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mirit I. Aladjem .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Marks, A.B., Fu, H., Aladjem, M.I. (2017). Regulation of Replication Origins. In: Masai, H., Foiani, M. (eds) DNA Replication. Advances in Experimental Medicine and Biology, vol 1042. Springer, Singapore. https://doi.org/10.1007/978-981-10-6955-0_2

Download citation

Publish with us

Policies and ethics