S Phase Progression in Human Cells Is Dictated by the Genetic Continuity of DNA Foci 英文参考文献.docVIP

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S Phase Progression in Human Cells Is Dictated by the Genetic Continuity of DNA Foci 英文参考文献.doc

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S Phase Progression in Human Cells Is Dictated by the Genetic Continuity of DNA Foci 英文参考文献

SPhaseProgressioninHumanCellsIsDictatedbythe GeneticContinuityofDNAFoci ApolinarMaya-Mendoza,PedroOlivares-Chauvet,AlexShaw,DeanA.Jackson* FacultyofLifeSciences,UniversityofManchester,Manchester,UnitedKingdom Abstract DNA synthesis must be performed with extreme precision to maintain genomic integrity. In mammalian cells, different genomicregionsarereplicatedatdefinedtimes,perhapstopreserveepigeneticinformationandcelldifferentiationstatus. However, the molecular principles that define this S phase program are unknown. By analyzing replication foci within discrete chromosome territories during interphase, we show that foci which are active during consecutive intervals of S phasearemaintainedasspatiallyadjacentneighborsthroughoutthecellcycle.UsingextendedDNAfibers,wedemonstrate that this spatial continuity of replication foci correlates with the genetic continuity of adjacent replicon clusters along chromosomes.Finally,weusedbioinformatictoolstocomparethestructureofDNAfociwithDNAdomainsthatareseento replicate during discrete time intervals of S phase using genome-wide strategies. Data presented show that a major mechanism of S phase progression involves the sequential synthesis of regions of the genome because of their genetic continuityalongthechromosomalfiber. Citation:Maya-MendozaA,Olivares-ChauvetP,ShawA,JacksonDA(2010)SPhaseProgressioninHumanCellsIsDictatedbytheGeneticContinuityofDNA Foci.PLoSGenet6(4):e1000900.doi:10.1371/journal.pgen.1000900 Editor:JeannieT.Lee,MassachusettsGeneralHospital,HowardHughesMedicalInstitute,UnitedStatesofAmerica ReceivedApril16,2009;AcceptedMarch8,2010;PublishedApril8,2010 Copyright:?2010Maya-Mendozaetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This research was supported by TheBiotechnologyandBiological Sciences ResearchCouncil(grant BBS/B/06091AM-M, DAJ), TheW