title: Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells.
abstract: Ionizing radiation induces a diverse spectrum of DNA lesions, including strand breaks and oxidized bases. In mammalian cells, ionizing radiation-induced lesions are targets of non-homologous end joining, homologous recombination, and base excision repair. In vitro assays show a potential involvement of DNA polymerase lambda in non-homologous end joining and base excision repair. In this study, we investigated whether DNA polymerase lambda played a significant role in determining ionizing radiation sensitivity. Despite increased sensitivity to hydrogen peroxide, lambda-deficient mouse embryonic fibroblasts displayed equal survival after exposure to ionizing radiation compared to their wild-type counterparts. In addition, we found increased sensitivity to the topoisomerase inhibitors camptothecin and etoposide in the absence of polymerase lambda. These results do not reveal a major role for DNA polymerase lambda in determining radiosensitivity in vivo.
authors: Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors: Christie
authors: C
authors: Vermeulen
authors: Barbara
authors: B
authors: Bertocci
authors: Adrian C
authors: AC
authors: Begg
authors: Conchita
authors: C
authors: Vens
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects; D019951:DNA Polymerase beta / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D016678:Genome / Q000235:genetics; D005838:Genotype; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
chemical_list: D005047:Etoposide; D006861:Hydrogen Peroxide; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta; D002166:Camptothecin