dRecQ4 Is Required for DNA Synthesis and Essential for Cell Proliferation in Drosophila 英文参考文献.docVIP

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dRecQ4 Is Required for DNA Synthesis and Essential for Cell Proliferation in Drosophila 英文参考文献.doc

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dRecQ4 Is Required for DNA Synthesis and Essential for Cell Proliferation in Drosophila 英文参考文献

dRecQ4IsRequiredforDNASynthesisandEssentialfor CellProliferationinDrosophila YanjuanXu1,2,ZhiyongLei1¤,HaiHuang1,2,WenDui1,2,XuehongLiang1, JunMa1,3,RenjieJiao1* 1StateKeyLaboratoryofBrainandCognitiveScience,InstituteofBiophysics,theChineseAcademyofSciences,Beijing,China,2GraduateSchooloftheChineseAcademy ofSciences,Beijing,China,3DivisionsofBiomedicalInformaticsandDevelopmentalBiology,CincinnatiChildren’sHospitalResearchFoundation,Cincinnati,Ohio,United StatesofAmerica Abstract Background:ThefamilyofRecQDNAhelicasesplaysanimportantroleinthemaintenanceofgenomicintegrity.Mutations inthreeofthefiveknownRecQfamilymembersinhumans,BLM,WRNandRecQ4,leadtodisordersthatarecharacterized bypredispositiontocancerandprematureaging. Methodology/Principal Findings: To address the in vivo functions of Drosophila RecQ4 (dRecQ4), we generated mutant allelesofdRecQ4usingthetargetedgeneknock-outtechnique.OurdatashowthatdRecQ4mutantsarehomozygouslethal withdefectsinDNAreplication,cellcycleprogressionandcellproliferation.TwosetsofexperimentssuggestthatdRecQ4 alsoplaysaroleinDNAdoublestrandbreakrepair.First,mutantanimalsexhibitsensitivitytogammairradiation.Second, the efficiency of DsRed reconstitution via single strand annealing repair is significantly reduced in the dRecQ4 mutant animals. Rescue experiments further show that both the N-terminal domain and the helicase domain are essential to dRecQ4functioninvivo.TheN-terminaldomainissufficientfortheDNArepairfunctionofdRecQ4. Conclusions/Significance:Together,ourresultsshowthatdRecQ4isanessentialgenethatplaysanimportantroleinnot onlyDNAreplicationbutalsoDNArepairandcellcycleprogressioninvivo. Citation:XuY,LeiZ,HuangH,DuiW,LiangX,etal.(2009)dRecQ4IsRequiredforDNASynthesisandEssentialforCellProliferationinDrosophila.PLoSONE4(7): e6107.doi:10.1371/journal.pone.0006107 Editor:Anja-KatrinBielinsky,UniversityofMinnesota,UnitedStatesofAmerica ReceivedApril13,2009;AcceptedJune2,2009;PublishedJuly2,2009 Copyright:?2009Xuetal.Thisisanopen