Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites.

ABSTRACT: The Nijmegen breakage syndrome protein Nbs1 is a component of the MRN (Mre11-Rad50-Nbs1) complex, central to the DNA damage response. While Nbs1 is generally believed to encompass a forkhead-associated domain linked to a breast cancer C-terminal (BRCT) domain, to date there is no experimental information on its three-dimensional structure. Through nuclear magnetic resonance (NMR) three-dimensional structure determination, we demonstrate that there is a second BRCT domain (BRCT2) in Nbs1. The domain has the characteristic BRCT topology, but with a long insertion shown to be flexible by NMR relaxation measurements. In the absence of sequence similarity to other proteins, a search for structural analogs of BRCT2 returned the second BRCT domain of the tandem BRCT repeats of cell cycle checkpoi

SUBMITTER: Xu C 

PROVIDER: S-EPMC2574983 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature