Dual role of Nbs1 in the ataxia telangiectasia mutated-dependent DNA damage response

The Nbs1 protein associates with Mre11 and Rad50 proteins to form the Mre11-Rad50-Nbs1 complex, which plays an important role in the intracellular signaling pathway activated in response to DNA damage. Mutations in the genes for each of these three components of the Mre11-Rad50-Nbs1 complex result in human diseases characterized by genomic instability. Insight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase, ataxia telangiectasia mutated, has been provided by recent studies. Nbs1 acts both as a downstream target of ataxia telangiectasia mutated in the S-phase checkpoint of the cell cycle as well as an upstream modulator or activator of ataxia telangiectasia mutated in the DNA damage response.