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.