Altered hematopoiesis in mice lacking DNA polymerase mu is due to inefficient double-strand break repair.
Polymerase micro (Polmicro) is an error-prone, DNA-directed DNA polymerase that participates in non-homologous end-joining (NHEJ) repair. In vivo, Polmicro deficiency results in impaired Vkappa-Jkappa recombination and altered somatic hypermutation and centroblast development. In Polmicro(-/-) 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 gamma-irradiation revealed that Polmicro also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polmicro 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.
Lucas
Daniel
D
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Escudero
Beatriz
B
Ligos
José Manuel
JM
Segovia
Jose Carlos
JC
Estrada
Juan Camilo
JC
Terrados
Gloria
G
Blanco
Luis
L
Samper
Enrique
E
Bernad
Antonio
A
D000818:Animals; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase