Effect of DNA Ligase IV Deficiency on Muagenesis with Alleilic Losses in FM3A cells

Abstract

In mammalian cells there are two major pathways for spontaneously arising and ionizing radiation (IR) induced DNA double strand breaks: homologous recombination (HR) and non-homologous end-joining (NHEJ). While a deficiency in any step of either pathway could render cells hypersensitive to IR, the resultant effect on mutations with allelic losses has not been fully understood. We measured spontaneous and X-ray induced mutagenesis with LOH in DNA ligase IV deficient SX10 cells and its parental SR-1 cells both heterozygously inactivated at the aprt locus. In SX10 cells, spontaneous mutation frequency was clearly higher than in the parental SR-1 cells. The mutation frequencies were not significantly elevated after X-irradiation in SX10, whereas a dose dependent increase was noted for SR-1. [J Radiat Res 44:412 (2003)]