Abstract
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, immunodeficiency, growth retardation, and cancer predisposition. Cells from NBS patients exhibit radiosensitivity, S-phase checkpoint defect, and chromosome instability. The gene product mutated in NBS, NBS1, forms a complex with MRE11 and RAD50 that is involved in the repair of DNA double-strand breaks (DSBs) and DNA damage checkpoints. DSBs are repaired by two major pathways, namely, homologous recombination (HR)-mediated repair (HRR) and nonhomologous end-joining (NHEJ). It has been reported that NBS1 functions in both HRR and NHEJ. However, the function of NBS1 in these processes has not been fully elucidated.
We have been focused on the function of NBS1 in HRR. In the screening of NBS1-interacting proteins, we found that RAD51, a key player in HRR, interacted with NBS1. The mutant NBS1 that lacks MRE11-binding domain failed to interact with RAD51, suggesting that NBS1 bound to RAD51 through MRE11.
Using an immunoprecipitation-based method, we searched RAD51-binding sites in MRE11, and found that MRE11 had two binding sites. We are now studying about these sites to elucidate the molecular function of them. We will report the results of these analyses.
