Recognition of Double Strand Breaks by a Mutator Protein (MU2) in Drosophila melanogaster 英文参考文献.docVIP

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Recognition of Double Strand Breaks by a Mutator Protein (MU2) in Drosophila melanogaster 英文参考文献.doc

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Recognition of Double Strand Breaks by a Mutator Protein (MU2) in Drosophila melanogaster 英文参考文献

RecognitionofDoubleStrandBreaksbyaMutator Protein(MU2)inDrosophilamelanogaster RaghuvarDronamraju,JamesM.Mason* LaboratoryofMolecularGenetics,NationalInstituteofEnvironmentalHealthSciences,ResearchTrianglePark,NorthCarolina,UnitedStatesofAmerica Abstract Telomere capture, a rare event that stabilizes chromosome breaks, is associated with certain genetic abnormalities in humans. Studies pertaining to the generation, maintenance, and biological effects of telomere formation are limited in metazoans. A mutation, mu2a, in Drosophila melanogaster decreases the rate of repair of double strand DNA breaks in oocytes,thusleadingtochromosomesthathavelostanaturaltelomereandgainedanewtelomere.Aminoacidsequence, domain architecture, and protein interactions suggest that MU2 is an ortholog of human MDC1. The MU2 protein is a componentofmeioticrecombinationfociandlocalizestorepairfociinS2cellsafterirradiationinamannersimilartothatof phosphorylatedhistonevariantH2Av.DomainsearchesindicatedthattheproteincontainsanN-terminalFHAdomainand aC-terminaltandemBRCTdomain.Peptidepull-downstudiesshowedthattheBRCTdomaininteractswithphosphorylated H2Av,whiletheFHAdomaininteractswiththecomplexofMRE11,RAD50,andNBS.Aframeshiftmutationthateliminates theMU2BRCTdomaindecreasesthenumberandsizeofmeioticphospho-H2Avfoci.MU2isalsorequiredfortheintra-S checkpointineye-antennalimaginaldiscs.MU2participatesatanearlystageintherecognitionofDNAdamageatastep that is prerequisite for both DNA repair and cell cycle checkpoint control. We propose a model suggesting that neotelomeresmayarisewhenradiation-inducedchromosomebreaksfailtoberepaired,failtoarrestprogressionthrough meiosis,andaredepositedinthezygote,wherecellcyclecontrolisabsentandrapidroundsofreplicationandtelomere formationensue. Citation: Dronamraju R, Mason JM (2009) Recognition of Double Strand Breaks by a Mutator Protein (MU2) in Drosophila melanogaster. PLoS Genet 5(5): e1000473.doi:10.1371/journal.pgen.1000473 Editor:R.ScottHawley,StowersInstitut