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Title

Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair

AuthorsLucas, Daniel; Escudero, Beatriz; Ligos, José Manuel; Segovia, José Carlos; Estrada, Juan Camilo; Terrados, Gloria ; Blanco, Luis ; Samper, Enrique; Bernad, Antonio
Issue DateFeb-2009
PublisherPublic Library of Science
CitationPLoS Genetics 5(2): e1000389
AbstractPolymerase mu (Polμ) is an error-prone, DNA-directed DNA polymerase that participates in non-homologous end-joining (NHEJ) repair. In vivo, Polμ deficiency results in impaired Vκ-Jκ recombination and altered somatic hypermutation and centroblast development. In Polμ−/− mice, hematopoietic development was defective in several peripheral and bone marrow (BM) cell populations, with about a 40% decrease in BM cell number that affected several hematopoietic lineages. Hematopoietic progenitors were reduced both in number and in expansion potential. The observed phenotype correlates with a reduced efficiency in DNA double-strand break (DSB) repair in hematopoietic tissue. Whole-body γ-irradiation revealed that Polμ also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polμ function is required for physiological hematopoietic development with an important role in maintaining early progenitor cell homeostasis and genetic stability in hematopoietic and non-hematopoietic tissues.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pgen.1000389
URIhttp://hdl.handle.net/10261/12235
DOIdoi:10.1371/journal.pgen.1000389
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