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

Jeroen Essers, Harry Van Steeg, Jan De Wit, Sigrid M.A. Swagemakers, Marcel Vermeij, Jan H.J. Hoeijmakers, Roland Kanaar

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

211 Citaten (Scopus)


Ionizing radiation and interstrand DNA crosslinking compounds provide important treatments against cancer due to their extreme genotoxicity for proliferating cells. Both the efficacies of such treatments and the mutagenic potential of these agents are modulated by the ability of cells to repair the inflicted DNA damage. Here we demonstrate that homologous recombination-deficient mRAD54(-/-) mice are hypersensitive to ionizing radiation at the embryonic but, unexpectedly, not at the adult stage. However, at the adult stage mRAD54 deficiency dramatically aggravates the ionizing radiation sensitivity of severe combined immune deficiency (scid) mice that are impaired in DNA double-strand break repair through DNA end-joining. In contrast, regardless of developmental stage, mRAD54(-/-) mice are hypersensitive to the interstrand DNA crosslinking compound mitomycin C. These results demonstrate that the two major DNA double-strand break repair pathways in mammals have overlapping as well as specialized roles, and that the relative contribution of these pathways towards repair of ionizing radiation-induced DNA damage changes during development of the animal.

Originele taal-2Engels
Pagina's (van-tot)1703-1710
Aantal pagina's8
TijdschriftEMBO Journal
Nummer van het tijdschrift7
StatusGepubliceerd - 3 apr. 2000
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Homologous and non-homologous recombination differentially affect DNA damage repair in mice'. Samen vormen ze een unieke vingerafdruk.

Citeer dit