NBN
NBN (nibrin, also known as NBS1, NBS, ATV, AT-V1 and AT-V2) is a component of the MRN complex, which repairs DNA double-strand breaks, maintains telomere integrity and supports meiosis. Within the complex it acts as a protein-protein adapter that recruits repair factors to damaged DNA. Browse Assay Genie's current range of NBN research reagents below, or read on for the biology behind the target.
NBN is a member of the MRN complex, together with MRE11 and RAD50. The complex plays a central role in double-strand break (DSB) repair, DNA recombination, telomere maintenance and meiosis. It contributes to error-free repair by homologous recombination, which occurs mainly in S and G2 phases, by mediating end resection of damaged DNA to generate single-stranded DNA. It is also required for the recruitment of other repair factors and for efficient activation of ATM and ATR after DNA damage. The nuclease activities of the complex, single-strand endonuclease and double-strand-specific 3'-5' exonuclease, are provided by MRE11.
Within the complex, NBN acts as an adapter that specifically recognises and binds phosphorylated proteins and promotes their recruitment to DNA damage sites. It recruits MRE11 and RAD50 to DSBs, promotes recruitment of the PI3/PI4-kinase family members ATM, ATR and probably DNA-PKcs, and mediates recruitment of phosphorylated RBBP8/CtIP, which promotes the endonuclease activity of the MRN complex to clear DNA ends carrying protein adducts. The MRN complex is also required for processing R-loops. NBN further enhances AKT1 phosphorylation, possibly through association with the mTORC2 complex.
At telomeres, NBN contributes to length maintenance through its interaction with TERF2, which during G1 phase prevents recruitment of DCLRE1B/Apollo. It also influences repair choice at dysfunctional telomeres: CDK2-phosphorylated NBN promotes non-homologous end joining, while unphosphorylated NBN promotes microhomology-mediated end-joining. Mutations in the NBN gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterised by microcephaly, growth retardation, immunodeficiency and cancer predisposition. The former HGNC name was Nijmegen breakage syndrome 1 (nibrin). The mouse and rat orthologues are both named Nbn.
NBN recruits MRE11, RAD50 and kinases such as ATM and ATR to breaks, making it a key factor for studying homologous recombination and end resection.
Through TERF2 binding and its role in repair pathway choice, NBN is relevant to telomere length maintenance and the handling of dysfunctional telomeres.
NBN mutations are associated with Nijmegen breakage syndrome, which features microcephaly, growth retardation, immunodeficiency and cancer predisposition.
The MRN complex is needed for efficient ATM and ATR activation, linking NBN to DNA damage-induced checkpoint activation.
NBN is a component of the MRN complex and acts as an adapter that binds phosphorylated proteins and recruits them to DNA damage sites. It brings MRE11, RAD50, ATM, ATR and CtIP to double-strand breaks, supporting end resection and homologous recombination repair.
The nibrin gene symbol NBN was previously Nijmegen breakage syndrome 1 (nibrin). Aliases include NBS1, NBS, ATV, AT-V1 and AT-V2. HGNC places it in the BRCA1 C complex and MRN complex gene groups, and UniProt classifies it in the Nibrin family.
Mouse and rat both carry an orthologous Nbn gene. In humans, NBN mutations are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability disorder. Check the datasheet of any product for its validated reactivity.
Other MRN complex members, DNA damage response kinases and telomere-associated proteins that work alongside NBN.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O60934; product specifications from Assay Genie datasheets.