A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in Homologous Recombination in C. elegans 英文参考文献.docVIP

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A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in Homologous Recombination in C. elegans 英文参考文献.doc

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A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in Homologous Recombination in C. elegans 英文参考文献

ANewThermosensitivesmc-3AlleleReveals InvolvementofCohesininHomologousRecombination inC.elegans AntoineBaudrimont1,AlexandraPenkner1,AlexanderWoglar1,YasmineM.Mamnun1,MargotHulek1, CathrinStruck2,RalfSchnabel2,JosefLoidl1,VerenaJantsch1* 1MaxF.PerutzLaboratories,DepartmentofChromosomeBiology,UniversityofVienna,Vienna,Austria,2DepartmentofGenetics,TechnicalUniversityofBraunschweig, Braunschweig,Germany Abstract The cohesin complex is required for the cohesion of sister chromatids and for correct segregation during mitosis and meiosis. Crossover recombination, together with cohesion, is essential for the disjunction of homologous chromosomes duringthefirstmeioticdivision.CohesinhasbeenimplicatedinfacilitatingrecombinationalrepairofDNAlesionsviathe sisterchromatid.Here,wemadeuseofanewtemperature-sensitivemutationintheCaenorhabditiselegansSMC-3protein tostudytheroleofcohesinintherepairofDNAdouble-strandbreaks(DSBs)andhenceinmeioticcrossingover.Wereport that attenuation of cohesin was associated with extensive SPO-11–dependent chromosome fragmentation, which is representative of unrepaired DSBs. We also found that attenuated cohesin likely increased the number of DSBs and eliminatedtheneedofMRE-11andRAD-50forDSBformationinC.elegans,whichsuggestsarolefortheMRNcomplexin makingcohesin-loadedchromatinsusceptibletomeioticDSBs.Notably,inspiteoflargelyintactsisterchromatidcohesion, backupDSBrepairviathesisterchromatidwasmostlyimpaired.Wealsofoundthatweakenedcohesinsaffectedmitotic repair of DSBs by homologous recombination, whereas NHEJ repair was not affected. Our data suggest that recombinationalDNArepairmakeshigherdemandsoncohesinsthandoeschromosomesegregation. Citation: Baudrimont A, Penkner A, Woglar A, Mamnun YM, Hulek M, et al. (2011) A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in HomologousRecombinationinC.elegans.PLoSONE6(9):e24799.doi:10.1371/journal.pone.0024799 Editor:MichaelPolymenis,TexasAMUniversity,UnitedStatesofAmerica ReceivedJune14,2