DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes 英文参考文献.docVIP

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DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes 英文参考文献.doc

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DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes 英文参考文献

DNADoubleStrandBreaksbutNotInterstrand CrosslinksPreventProgressthroughMeiosisinFully GrownMouseOocytes WaiShanYuen1,JulieA.Merriman1,MoiraK.O’Bryan2,KeithT.Jones1* 1SchoolofBiomedicalSciencesandPharmacy,UniversityofNewcastle,Callaghan,NewSouthWales,Australia,2DepartmentofAnatomyandDevelopmentalBiology, MonashUniversity,Clayton,Victoria,Australia Abstract ThereissomeinterestinhowmammalianoocytesrespondtodifferenttypesofDNAdamagebecauseoftheincreasing expectationoffertilitypreservationinwomenundergoingchemotherapy.Doublestrandbreaks(DSBs)inducedbyionizing radiationandagentssuchasneocarzinostatin(NCS),andinterstrandcrosslinks(ICLs)inducedbyalkylatingagentssuchas mitomycinC(MMC),aretoxicDNAlesionsthatneedtoberepairedforcellsurvival.HereweexaminedtheeffectsofNCS andMMCtreatmentonoocytescollectedfromantralfolliclesinmice,becausepotentiallysuchoocytesarereadilycollected fromovariesanddonotneedtobeinvitrogrowntoachievemeioticcompetency.Wefoundthatoocytesweresensitiveto NCS, such that this ionizing radiation mimetic blocked meiosis I and caused fragmented DNA. In contrast, MMC had no impactonthecompletionofeithermeiosisIorII,evenatextremelyhighdoses.However,oocytestreatedwithMMCdid show c-H2AX foci and following their in vitro maturation and parthenogenetic activation the development of the subsequent embryos was severely compromised. Addition of MMC to 1-cell embryos caused a similarly poor level of development,demonstratingoocyteshaveeventualsensitivitytothisICL-inducingagentbutthisdoesnotoccurduring their meiotic division. In oocytes, the association of Fanconi Anemia protein, FANCD2, with sites of ICL lesions was not apparentuntilentryintotheembryoniccellcycle.Inconclusion,meioticmaturationofoocytesissensitivetoDSBsbutnot ICLs.TheabilityofoocytestotoleratesevereICLdamageandyetcompletemeiosis,meansthatthistypeofDNAlesiongoes unrepairedinoocytesbutimpactsonsubsequentembryoquality. Citation:YuenWS,MerrimanJA,O’BryanMK,JonesKT(2012)DNADoubleStrandBreaksbutNotInterstrandCr