Dual Roles for DNA Polymerase Theta in Alternative End-Joining Repair of Double-Strand Breaks in Drosophila 英文参考文献.docVIP

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Dual Roles for DNA Polymerase Theta in Alternative End-Joining Repair of Double-Strand Breaks in Drosophila 英文参考文献.doc

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Dual Roles for DNA Polymerase Theta in Alternative End-Joining Repair of Double-Strand Breaks in Drosophila 英文参考文献

DualRolesforDNAPolymeraseThetainAlternativeEnd- JoiningRepairofDouble-StrandBreaksinDrosophila SzeHamChan1.,AmyMarieYu1.,MitchMcVey1,2 * 1DepartmentofBiology,TuftsUniversity,Medford,Massachusetts,UnitedStatesofAmerica,2PrograminGenetics,TuftsSacklerSchoolofGraduateBiomedicalSciences, Boston,Massachusetts,UnitedStatesofAmerica Abstract DNAdouble-strandbreaksarerepairedbymultiplemechanismsthatareroughlygroupedintothecategoriesofhomology- directed repair and non-homologous end joining. End-joining repair can be further classified as either classical non- homologousendjoining,whichrequiresDNAligase4,or‘‘alternative’’endjoining,whichdoesnot.Alternativeendjoining hasbeenassociatedwithgenomicdeletionsandtranslocations,butitsmolecularmechanism(s)arelargelyuncharacterized. Here, we report that Drosophila melanogaster DNA polymerase theta (pol theta), encoded by the mus308 gene and previouslyimplicatedinDNAinterstrandcrosslinkrepair,playsacrucialroleinDNAligase4-independentalternativeend joining.Intheabsenceofpoltheta,endjoiningisimpairedandresidualrepairoftencreateslargedeletionsflankingthe breaksite.Analysisofbreakrepairjunctionsfromflieswithmus308separation-of-functionallelessuggeststhatpoltheta promotestheuseoflongmicrohomologiesduringalternativeendjoiningandincreasesthelikelihoodofcomplexinsertion events. Our results establish pol theta as a key protein in alternative end joining in Drosophila and suggest a potential mechanisticlinkbetweenalternativeendjoiningandinterstrandcrosslinkrepair. Citation:ChanSH,YuAM,McVeyM(2010)DualRolesforDNAPolymeraseThetainAlternativeEnd-JoiningRepairofDouble-StrandBreaksinDrosophila.PLoS Genet6(7):e1001005.doi:10.1371/journal.pgen.1001005 Editor:R.ScottHawley,StowersInstituteforMedicalResearch,UnitedStatesofAmerica ReceivedSeptember15,2009;AcceptedMay27,2010;PublishedJuly1,2010 Copyright: ? 2010 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestrictedus