Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair 英文参考文献.docVIP

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Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair 英文参考文献.doc

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Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair 英文参考文献

AlteredHematopoiesisinMiceLackingDNAPolymerase mIsDuetoInefficientDouble-StrandBreakRepair DanielLucas1¤,BeatrizEscudero2,Jose′ ManuelLigos2,JoseCarlosSegovia3,JuanCamiloEstrada2, GloriaTerrados4,LuisBlanco4,EnriqueSamper1,2,AntonioBernad1,2* 1Departamento de Inmunolog?′a y Oncolog?′a, Centro Nacional de Biotecnolog?′a, Consejo Superior de Investigaciones Cientificas, Campus Universidad Auto′noma de Madrid,Cantoblanco,Madrid,Spain,2DepartamentodeCardiolog?′aRegenerativa,UnidaddeCelo′mica,CentroNacionaldeInvestigacionesCardiovascularesCarlosIII, Madrid,Spain,3HematopoiesisandGeneTherapyDivision,CentrodeInvestigacionesEnerge′ticas,Medioambientales,yTecnolo′gicas,CentrodeInvestigacio′nBiome′dica en Red de Enfermedades Raras, Madrid, Spain, 4Centro de Biolog?′a Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Campus Universidad Auto′nomadeMadrid,Cantoblanco,Madrid,Spain Abstract Polymerasemu(Polm)isanerror-prone,DNA-directedDNApolymerasethatparticipatesinnon-homologousend-joining (NHEJ) repair. In vivo, Polm deficiency results in impaired Vk-Jk recombination and altered somatic hypermutation and centroblast development. In Polm2/2 mice, hematopoietic development was defective in several peripheral and bone marrow(BM)cellpopulations,withabouta40%decreaseinBMcellnumberthataffectedseveralhematopoieticlineages. Hematopoieticprogenitorswerereducedbothinnumberandinexpansionpotential.Theobservedphenotypecorrelates with a reduced efficiency in DNA double-strand break (DSB) repair in hematopoietic tissue. Whole-body c-irradiation revealed that Polm also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polm function is required for physiological hematopoietic development with an important role in maintaining early progenitor cell homeostasisandgeneticstabilityinhematopoieticandnon-hematopoietictissues. Citation: Lucas D, Escudero B, Ligos JM, Segovia JC, Estrada JC, et al. (2009) Altered Hematopoiesis in Mice Lacking DNA P