ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes 英文参考文献.docVIP

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ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes 英文参考文献.doc

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ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes 英文参考文献

ATMPromotestheObligateXYCrossoverandboth CrossoverControlandChromosomeAxisIntegrityon Autosomes MarcoBarchi1.¤a,IgnasiRoig2.,MonicaDiGiacomo2¤b,DirkG.deRooij3,4,ScottKeeney2,5* ,Maria Jasin1,5 * 1Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 2Molecular Biology Program, Memorial Sloan-KetteringCancerCenter,NewYork,NewYork,UnitedStatesofAmerica,3DepartmentofEndocrinologyandMetabolism,FacultyofScience,UtrechtUniversity,The Netherlands, 4Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands, 5Weill Graduate School of Medical Sciences of Cornell University,NewYork,NewYork,UnitedStatesofAmerica Abstract Duringmeiosisinmostsexuallyreproducingorganisms,recombinationformscrossoversbetweenhomologousmaternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understoodinmostorganisms,includingmammals.HereweprovideevidencethattheATMkinaseorproteinisessential forpropercrossoverformationinmousespermatocytes.ATMdeficiencycausesmultiplephenotypesinhumansandmice, including gonadal atrophy. Mouse Atm2/2 spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm2/2 meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meioticmetaphaseI.Strikingly,Spo11+/2Atm2/2spermatocytesaredefectiveinformingtheobligatecrossoveronthesex chromosomes,eventhoughtheXYpairisusuallyincorporatedinasexbodyandistranscriptionallyinactivatedasinnormal spermatocytes.TheXYcrossoverdefectcorrelateswiththeappearanceoflaggingchromosomesatmetaphaseI,whichmay trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distributionofcrossoversonautosomesappearstobedefectiveintheabsenceofATMbecausethereisanincreas