Homologous and non-homologous recombination differentially affect DNA damage repair in mice

Citation
J. Essers et al., Homologous and non-homologous recombination differentially affect DNA damage repair in mice, EMBO J, 19(7), 2000, pp. 1703-1710
Citations number
59
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
02614189 → ACNP
Volume
19
Issue
7
Year of publication
2000
Pages
1703 - 1710
Database
ISI
SICI code
0261-4189(20000403)19:7<1703:HANRDA>2.0.ZU;2-R
Abstract
Ionizing radiation and interstrand DNA crosslinking compounds provide impor tant treatments against cancer due to their extreme genotoxicity for prolif erating cells. Both the efficacies of such treatments and the mutagenic pot ential of these agents are modulated by the ability of cells to repair the inflicted DNA damage. Here we demonstrate that homologous recombination-def icient mRAD54(-/-) mice are hypersensitive to ionizing radiation at the emb ryonic but, unexpectedly, not at the adult stage. However, at the adult sta ge mRAD54 deficiency dramatically aggravates the ionizing radiation sensiti vity of severe combined immune deficiency (scid) mice that are impaired in DNA double-strand break repair through DNA end-joining. In contrast, regard less of developmental stage, mRAD54-/- mice are hypersensitive to the inter strand DNA crosslinking compound mitomycin C, These results demonstrate tha t the two major DNA double-strand break repair pathways in mammals have ove rlapping as well as specialized roles, and that the relative contribution o f these pathways towards repair of ionizing radiation-induced DNA damage ch anges during development of the animal.