NBS1 (Nijmegen breakage syndrome protein 1) is a component of the MRN complex (Mre11-Rad50-Nbs1) that plays important role in detecting DNA double strand breaks (DSBs) and triggering the downstream cascade. DSBs can be caused by ionizing radiation, chemotherapy drugs, metabolic ROS, replication errors, programmed enzymatic activities during meiosis/V(D)J recombination, etc. NBS1 acts as a DSB sensor, co-activator of DSB-induced cell cycle checkpoint signaling, and also the repair-effector via two competing DSB repair pathways - homologous recombination (HR) and non-homologous end-joining (NHEJ). The MRN complex also associates with telomeres at the terminal ends of linear chromosomes and contributes to their maintenance.
Through a forkhead-associated domain (FHA) domain, NBS1 binds phospho-Thr residues within the Ser-X-Thr motifs found in such DNA damage proteins as Mdc1 and Ctp1. Another domain type, the breast cancer C-terminal (BRCT), binds Ser-X-Thr motifs with phosphor-Ser residues. These interactions are phosphodependent and drive the recruitment of repair and checkpoint proteins to the DSB sites. NBS1 is also responsible for nuclear translocation of the MRN complex. Because of NBS1’s central role in coordinating DSB detection and repair, NBS1 antibody enables characterization of molecules within the DNA repair machinery. Use of the NBS1 antibody dissected out three distinct and functionally important radiation-induced autophosphorylation events in ataxia-telangiectasia mutated (ATM) (1). Zhang, et. al. employed the NBS1 antibody found that ATM signaling and proper function rely upon both antagonism and redundancy between NBS1 and the ATMIN protein (2). Furthermore, Gatei’s group demonstrated that Rad50 phosphorylation also plays a role in ATM-dependent downstream signaling to maintain genome integrity (3). The NBS1 antibody allowed Hsu, et. al. to create expression profiles of oral sqaumous cell carcinomas and NBS1 appears to be a strong candidate as a prognostic marker (4). Intriguing work from Ou’s lab with the NBS1 antibody at the Salk Institute also suggests that the adenoviral E4-ORF3 forms a nuclear polymer that consists of an efficient and multivalent matrix capable of trapping and inactivating a wide variety of tumor suppressors (5).
Novus Biologicals offers various NBS1 reagents for your research needs including:
