|Application ||WB, IHC|
|Calculated MW||84959 Da|
|Other Names||Nibrin, Cell cycle regulatory protein p95, Nijmegen breakage syndrome protein 1, NBN, NBS, NBS1, P95|
|Target/Specificity||A phospho-specific peptide corresponding to residues surrounding serine 432 of human p95/NSB1 was used as an immunogen. This antibody detects p95/NSB1 that is phosphorylated on serine 432.|
|Format||50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.|
|Precautions||p95 NBS1 Antibody Phospho (pS432) is for research use only and not for use in diagnostic or therapeutic procedures.|
|Synonyms||NBS, NBS1, P95|
|Function||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.|
|Cellular Location||Nucleus. Nucleus, PML body. Chromosome, telomere Note=Localizes to discrete nuclear foci after treatment with genotoxic agents.|
|Tissue Location||Ubiquitous. Expressed at high levels in testis|
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Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer. p95/NBS1 is specifically phosphorylated in response to gamma-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of p95/NBS1 mediated by gamma-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. Phosphorylation of p95/NBS1 by ATM is critical for certain responses of human cells to DNA damage (1). p95/NBS1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Observations link ATM and p95/NBS1 in a common signaling pathway and provide an explanation for phenotypic similarities in NBS and ATM diseases (2). Double-strand breaks occur during DNA replication and are also induced by ionizing radiation. NBS1 is essential for homologous recombination-mediated repair in higher vertebrate cells and the disruption of p95/NBS1 reduces gene conversion and sister chromatid exchanges (3).
1. Wu X, et al. Nature 405(6785):404-5, 2000
2. Lim DS, et al. Nature 404(6778):613-7, 2000
3. Tauchi H, et al. Nature 420(6911):93-8, 2002
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