Analysis of apoptosis induction pathway dependent on Nbs1

Abstract

DNA double strand break (DSB) is the most critical damage that are induced by radiation. Many DSB repair proteins have been identified using several approaches such as positional cloning and phenotype analysis of knockout cells. Among these, Nbs1, the underlying gene for Nijmegen breakage syndrome, forms a complex with Mre11/Rad50 and is essential for homologous recombination (HR) and S-phase check point. To clarify the role of Nbs1 protein on DSB responding pathways, we analyzed apoptosis induction in Nbs1 deficient cells after irradiation. In sharp contrast to wild type cells, NBS1 deficient cells did not display apparent induction of apoptosis after exposure to X-rays. Because DT40 cells are not expressing p53, our results suggest that Nbs1 acts in a critical pathway for induction of apoptosis independent of p53. We report results from the analysis of Nbs1-dependent but p53-independent pathways for apoptosis induction.