Interaction between Nbs1 and Ku70 for DNA damage response

Abstract

NBS1 is the responsible gene for Nijmegen breakage syndrome which patients display cancer predisposition and hyper-sensitivity to ionizing radiation, NBS1 is known to from a complex with MRE11 and Rad50, and it regulates the precise repair of damaged DNA through homologous recombination. We reported that NBS1 activates a p53-independent apoptotic pathway in response to DNA damage through the regulation of the dissociation of Ku70-Bax complex. The phosphorylation at 343-serine residue of NBS1 was essential for this function, whereas FHA, MRE11-binding, or ATM interacting domains were not. The kinase toward this NBS1 phosphorylation could be ATR because ATR inhibitor suppressed the NBS1 phosphorylation at the time when apoptosis occurring. but ATM inhibitor did not.
To get insight of the interaction between NBS1 and Ku70, we successfully established a Nbs1-Ku70 double Knockout cell line. In this presentation, we will discuss about the phenotypes of the Nbs1-Ku70 double knockout cells and the function of the interaction between NBS1 and Ku70 in DNA damage response induced by ionizing radiation.