AFfirm™ p95/NBS1 Mouse Monoclonal Antibody - #BF8411

Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex.

Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.

Nucleus. Nucleus>PML body. Chromosome>Telomere. Chromosome.
Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.

Ubiquitous. Expressed at high levels in testis.

Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN. As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN. Interacts with histone H2AX this requires phosphorylation of H2AX on 'Ser-139'. Interacts with HJURP. Interacts with INTS3. Interacts with KPNA2. Interacts with TERF2. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection. Interacts with SP100; recruits NBN to PML bodies. Interacts with ATF2. Interacts with MTOR, MAPKAP1 isoform 2 and RICTOR; indicative for an association with the mTORC2 complex. Interacts with MRNIP.

(Microbial infection) Interacts with herpes simplex virus 1 protein UL12.

The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage.

The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.

The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.