Description
NBS1 (Nijmegen breakage syndrome protein 1, Nibrin) is the eukaryotic component of
MRN complex (Mre11-Rad50-Nbs1) involved in
homologous recombination repair for
DNA double-strand breaks (DSBs) and DNA damage-induced checkpoint activation. NBS1, a nuclear protein with a theoretical molecular weight of 65-85 kDa, is composed of 2 functional regions: the forkhead associated (FHA) N-terminal domain (24-83 amino acids) and the breast cancer C-terminus (BRCT) domain (105-181 amino acids). Mutations in the NBN gene are associated with Nijmegen breakage syndrome, characterized by microcephaly, growth retardation, immunodeficiency, and an increased susceptibility to
prostate cancer, lung cancer, liver cancer and intrahepatic cholangiocarcinoma (IHC) (1).
In DNA double strand break repair, the FHA/BRCT domains bind DNA damage sensor proteins including gamma H2AX (phospho Ser139), phosphorylated
MDC1 and
CtIP (CtBP-interacting protein). NBS1 then recruits the other members of the MRN complex,
Mre11 and
Rad50, to the proximity of DNA DSBs. The MRN complex has also been shown to interact with
ATM or
ATR kinases in the presence of DSBs or replication fork stalling, respectively. Phosphorylation of NBS1 at Ser 278 and Ser343 in response to ionizing radiation (IR) is dependent on ATM and is important for activation of the S phase checkpoint. The activation of ATM in response to DNA damage is also facilitated by MRN and may lead to induction of
apoptosis (2, 3).
References
1. Bian L, Meng Y, Zhang M, Li D. (2019) MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol Cancer. 26;18(1):169. PMID: 31767017
2. Zhang Y, Zhou J, Lim CU. (2006) The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res. 16(1):45-54. PMID: 16467875
3. Komatsu K. NBS1 and multiple regulations of DNA damage response. (2016) J Radiat Res. 57 Suppl 1:i11-i17. PMID: 27068998
Bioinformatics
| Uniprot |
Human
Human
Human
Human
Mouse
|
| Product By Gene ID |
4683 |
| Alternate Names |
- ATV
- AT-V1
- AT-V2
- Cell cycle regulatory protein p95
- FLJ10155
- MGC87362
- NBS
- NBS1P95
- nibrin
- Nijmegen breakage syndrome 1 (nibrin)
- Nijmegen breakage syndrome protein 1
- p95 protein of the MRE11/RAD50 complex
- p95
|
