Preferential Re-Replication of Drosophila Heterochromatin in the Absence of Geminin 英文参考文献.docVIP
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Preferential Re-Replication of Drosophila Heterochromatin in the Absence of Geminin 英文参考文献
PreferentialRe-ReplicationofDrosophila
HeterochromatinintheAbsenceofGeminin
QueyingDing,DavidM.MacAlpine*
DepartmentofPharmacologyandCancerBiology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica
Abstract
Toensuregenomicintegrity,thegenomemustbeduplicatedexactlyoncepercellcycle.Disruptionofreplicationlicensing
mechanismsmayleadtore-replicationandgenomicinstability.Cdt1,alsoknownasDouble-parked(Dup)inDrosophila,isa
keyregulatoroftheassembly ofthepre-replicative complex(pre-RC)anditsactivityisstrictlylimitedtoG1 bymultiple
mechanismsincludingCul4-Ddb1mediatedproteolysisandinhibitionbygeminin.Weassayedthegenomicconsequences
of disregulating the replication licensing mechanisms by RNAi depletion of geminin. We found that not all origins of
replicationweresensitivetogeminindepletionandthatheterochromaticsequenceswerepreferentiallyre-replicatedinthe
absenceoflicensingmechanisms.Thepreferentialre-activationofheterochromaticoriginsofreplicationwasunexpected
becausethesearetypicallythelastsequencestobeduplicatedinanormalcellcycle.Wefoundthatthere-replicationof
heterochromatinwasregulatednotatthelevelofpre-RCactivation,butratherbytheformationofthepre-RC.Unlikethe
global assembly of the pre-RC that occurs throughout the genome in G1, in the absence of geminin, limited pre-RC
assembly was restricted to the heterochromatin by elevated cyclin A-CDK activity. These results suggest that there are
chromatinandcellcyclespecificcontrolsthatregulatethere-assemblyofthepre-RCoutsideofG1.
Citation: Ding Q, MacAlpine DM (2010) Preferential Re-Replication of Drosophila Heterochromatin in the Absence of Geminin. PLoS Genet 6(9): e1001112.
doi:10.1371/journal.pgen.1001112
Editor:ChristopherE.Pearson,TheHospitalforSickChildrenandUniversityofToronto,Canada
ReceivedMarch17,2010;AcceptedAugust5,2010;PublishedSeptember9,2010
Copyright: ?2010Ding,MacAlpine.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits
unrestrict
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