title: The spatial and temporal organization of origin firing during the S-phase of fission yeast.
abstract: Eukaryotes duplicate their genomes using multiple replication origins, but the organization of origin firing along chromosomes and during S-phase is not well understood. Using fission yeast, we report the first genome-wide analysis of the spatial and temporal organization of replication origin firing, analyzed using single DNA molecules that can approach the full length of chromosomes. At S-phase onset, origins fire randomly and sparsely throughout the chromosomes. Later in S-phase, clusters of fired origins appear embedded in the sparser regions, which form the basis of nuclear replication foci. The formation of clusters requires proper histone methylation and acetylation, and their locations are not inherited between cell cycles. The rate of origin firing increases gradually, peaking just before mid S-phase. Toward the end of S-phase, nearly all the available origins within the unreplicated regions are fired, contributing to the timely completion of genome replication. We propose that the majority of origins do not fire as a part of a deterministic program. Instead, origin firing, both individually and as clusters, should be viewed as being mostly stochastic.
authors: The Rockefeller University, New York, New York 10065, USA; kaykova@rockefeller.edu.
authors: Atanas
authors: A
authors: Kaykov
authors: The Rockefeller University, New York, New York 10065, USA; The Francis Crick Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, United Kingdom.
authors: Paul
authors: P
authors: Nurse
mesh_terms: D015825:Chromosomes, Fungal; D004261:DNA Replication; D004271:DNA, Fungal; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005810:Multigene Family; D009154:Mutation; D018741:Replication Origin; D016196:S Phase / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics*
chemical_list: D004271:DNA, Fungal
references: EMBO J. 2007 Mar 7;26(5):1315-26
references: 17304223
references: J Cell Biol. 1998 Mar 23;140(6):1285-95
references: 9508763
references: Nature. 2004 Jul 15;430(6997):372-6
references: 15254542
references: Genes Dev. 2012 Sep 15;26(18):2050-62
references: 22987637
references: Nature. 2007 Jun 14;447(7146):799-816
references: 17571346
references: Nucleic Acids Res. 2008 Oct;36(17):5623-34
references: 18765475
references: J Cell Biol. 2013 Sep 30;202(7):1001-12
references: 24062338
references: Nucleic Acids Res. 1989 Apr 11;17(7):2801-18
references: 2785683
references: Mol Cell. 2002 Nov;10(5):1223-33
references: 12453428
references: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):337-42
references: 15623550
references: Genes Dev. 2009 May 1;23(9):1077-90
references: 19417103
references: EMBO J. 2011 Nov 30;30(23):4805-14
references: 22081107
references: Mol Biol Cell. 2008 Dec;19(12):5550-8
references: 18799612
references: Nat Rev Mol Cell Biol. 2010 Oct;11(10):728-38
references: 20861881
references: Science. 1997 Sep 5;277(5331):1518-23
references: 9278517
references: Genes Dev. 2002 Oct 1;16(19):2479-84
references: 12368258
references: Nat Cell Biol. 2006 Dec;8(12):1313-6
references: 17139278
references: EMBO J. 2007 Mar 7;26(5):1327-39
references: 17304213
references: Genome Biol Evol. 2011;3:799-811
references: 21666225
references: Annu Rev Biochem. 2002;71:333-74
references: 12045100
references: Chromosoma. 2014 Jun;123(3):183-99
references: 24337246
references: EMBO J. 2001 Nov 1;20(21):6115-26
references: 11689451
references: Curr Genet. 1984 Feb;8(2):93-7
references: 24177582
references: Genes Dev. 2012 Jan 15;26(2):137-50
references: 22279046
references: Mol Biol Cell. 2010 Feb 1;21(3):393-404
references: 19955211
references: EMBO J. 2006 Nov 1;25(21):5171-9
references: 17053780
references: Cell. 2013 Mar 28;153(1):178-92
references: 23523135
references: J Mol Biol. 2008 Jan 4;375(1):12-9
references: 17999930
references: Mol Biol Cell. 2006 Jan;17(1):308-16
references: 16251353
references: J Cell Biol. 2001 Jan 8;152(1):15-25
references: 11149917
references: Nature. 2002 Feb 21;415(6874):871-80
references: 11859360
references: Chromosome Res. 2010 Jan;18(1):91-102
references: 20039120
references: Methods Enzymol. 1991;194:795-823
references: 2005825
references: Nat Cell Biol. 2009 Mar;11(3):357-62
references: 19182789
references: PLoS Biol. 2012 Jul;10(7):e1001360
references: 22807655
references: Chromosoma. 2000 Mar;108(8):471-84
references: 10794569
references: Curr Top Dev Biol. 2006;76:129-84
references: 17118266
references: Cell. 2009 Mar 6;136(5):852-64
references: 19269364
references: PLoS One. 2009;4(6):e5899
references: 19521533