NBN
Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]
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.
Biological Process
Blastocyst growth Source: Ensembl
Cell population proliferation Source: Ensembl
DNA damage checkpoint signaling Source: MGI
DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
DNA double-strand break processing Source: ComplexPortal
DNA duplex unwinding Source: BHF-UCL
DNA strand resection involved in replication fork processing Source: ComplexPortal
Double-strand break repair Source: UniProtKB
Double-strand break repair via homologous recombination Source: GO_Central
Homologous recombination Source: ComplexPortal
Intrinsic apoptotic signaling pathway Source: Ensembl
Isotype switching Source: Ensembl
Meiotic cell cycle Source: UniProtKB-KW
Mitotic G2/M transition checkpoint Source: ComplexPortal
Mitotic G2 DNA damage checkpoint signaling Source: UniProtKB
Negative regulation of telomere capping Source: BHF-UCL
Neuromuscular process controlling balance Source: Ensembl
Positive regulation of kinase activity Source: BHF-UCL
Positive regulation of protein autophosphorylation Source: BHF-UCL
Positive regulation of telomere maintenance Source: BHF-UCL
Regulation of cell cycle Source: UniProtKB
Regulation of DNA-dependent DNA replication initiation Source: UniProtKB
T-circle formation Source: BHF-UCL
Telomere maintenance Source: UniProtKB
Telomere maintenance via telomere trimming Source: BHF-UCL
Telomeric 3' overhang formation Source: BHF-UCL
Cellular Location
Nucleus
PML body
Other locations
telomere
Chromosome
Note: Localizes to discrete nuclear foci after treatment with genotoxic agents (PubMed:26438602, PubMed:10783165, PubMed:26215093). Acetylation of 'Lys-5' of histone H2AX (H2AXK5ac) promotes NBN/NBS1 assembly at the sites of DNA damage (PubMed:26438602).
Involvement in disease
Nijmegen breakage syndrome (NBS):
A disorder characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies.
Breast cancer (BC):
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Aplastic anemia (AA):
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).
PTM
Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.
Loading...
Datasheet