Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection 英文参考文献.docVIP

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Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection 英文参考文献.doc

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Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection 英文参考文献

DistinctFunctionsfortheDrosophilapiRNAPathwayin GenomeMaintenanceandTelomereProtection JaspreetS.Khurana1,JiaXu2,ZhipingWeng3,WilliamE.Theurkauf1* 1PrograminCellandDevelopmentalDynamicsandPrograminMolecularMedicine,UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStates ofAmerica,2DepartmentofBiomedicalEngineering,BostonUniversity,Boston,Massachusetts,UnitedStatesofAmerica, 3PrograminBioinformaticsandIntegrative BiologyandDepartmentinBiochemistryandMolecularPharmacology,UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStatesofAmerica Abstract TransposonsandotherselfishDNAelementscanbefoundinallphyla,andmobilizationoftheseelementscancompromise genomeintegrity.ThepiRNA(PIWI-interactingRNA)pathwaysilencestransposonsinthegermline,butitisunclearifthis pathway has additional functions during development. Here we show that mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead to extensive fragmentation of the zygotic genome during the cleavage stage of embryonic divisions. Additionally, aub and armi show defects in telomere resolution during meiosis and the cleavage divisions; and mutations in lig-IV, which disrupt non-homologous end joining, suppress these fusions. By contrast, lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation studies show that aub and armi mutations disrupt telomere binding of HOAP, which is a component of the telomere protection complex, and reduce expressionofasubpopulationof19-to22-nttelomere-specificpiRNAs.Mutationsinrhiandago3,bycontrast,donotblock HOAP binding or production of these piRNAs. These findings uncover genetically separable functions for the Drosophila piRNA pathway. The aub, armi, rhi, and ago3 genes silence transposons and maintain chromosome integrity during cleavage-stage embryonic divisions. However, the aub and armi genes have an additional function in assembly of the telomereprotectioncomplex. Citation: Khurana JS, Xu J, We