The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Nbn  -  nibrin

Mus musculus

Synonyms: Cell cycle regulatory protein p95, Nbs1, Nibrin, Nijmegen breakage syndrome protein 1 homolog
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Nbn

  • This study gives insight into the physiological function of NBS1 (the Nbn gene product) and the function of the DNA damage response in the neurological anomalies of NBS, ataxia telangiectasia and ATLD [1].
  • Furthermore, Nbn-deficient neuroprogenitors show proliferation defects (but not increased apoptosis) and contain more chromosomal breaks, which are accompanied by ataxia telangiectasia mutated protein (ATM)-mediated p53 activation [1].
  • Moreover, gamma-irradiation enhanced tumor development in Nbn(+/-) mice, giving rise to a high frequency of epithelial tumors, mostly in the thyroid and lung, as well as lymphomas [2].
  • Cytogenetic analysis revealed that primary Nbn(+/-) embryonic fibroblasts and tumor cells exhibit increased chromosomal aberrations [2].
  • Unexpectedly, all Nbn-deficient lenses develop cataracts at an early age due to altered lens fibre cell differentiation, including disruption of normal lens epithelial and fibre cell architecture and incomplete denucleation of fibre cells, and these changes are independent of the p53 pathway [3].

High impact information on Nbn

  • Notably, depletion of p53 substantially rescues the neurological defects of Nbn mutant mice [1].
  • Loss of Nbn causes proliferation arrest of granule cell progenitors and apoptosis of postmitotic neurons in the cerebellum [1].
  • Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (gamma-H2AX, also known as gamma-H2afx), which facilitate DNA double-strand break (DSB) repair, form nuclear foci at the Ch region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX-/- mice [4].
  • Localization of Nbs1 and gamma-H2AX to the Igh locus during CSR is dependent on AID [4].
  • AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching [4].

Chemical compound and disease context of Nbn


Biological context of Nbn

  • Mdm2 co-localized with Nbs1 to sites of DNA damage following gamma-irradiation [6].
  • Here, we show by cell-type-specific conditional inactivation of Nbn, the murine homologue of NBS1, that nibrin plays a role in the repair of gamma-irradiation damage, maintenance of chromosomal stability, and the recombination of Ig constant region genes in B lymphocytes [7].
  • Induction of Nbn null mutation leads to the loss of the G2/M checkpoint, increased chromosome damage, radiomimetic-sensitivity and cell death [8].
  • Here, we have used Cre recombinase/loxP technology to generate an inducible Nbn null mutation allowing the examination of DNA-repair and cell cycle-checkpoints in the complete absence of nibrin [8].
  • These data suggest that haploinsufficiency, not loss of heterozygosity, of Nbn could be the mechanism underlying the tumor development [2].

Anatomical context of Nbn


Other interactions of Nbn


Analytical, diagnostic and therapeutic context of Nbn

  • To study the impact of NBS1 heterozygosity on malignancy susceptibility, we disrupted the murine homologue (Nbn) of NBS1 in mice using gene targeting techniques [2].
  • Southern and Western blot analyses showed a remaining wild-type allele and nibrin expression in Nbn(+/-) tumors [2].
  • Northern blotting revealed comparable levels of Nbn transcripts in most tissues in the mouse [9].


  1. An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Frappart, P.O., Tong, W.M., Demuth, I., Radovanovic, I., Herceg, Z., Aguzzi, A., Digweed, M., Wang, Z.Q. Nat. Med. (2005) [Pubmed]
  2. Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Dumon-Jones, V., Frappart, P.O., Tong, W.M., Sajithlal, G., Hulla, W., Schmid, G., Herceg, Z., Digweed, M., Wang, Z.Q. Cancer Res. (2003) [Pubmed]
  3. A novel function of DNA repair molecule Nbs1 in terminal differentiation of the lens fibre cells and cataractogenesis. Yang, Y.G., Frappart, P.O., Frappart, L., Wang, Z.Q., Tong, W.M. DNA Repair (Amst.) (2006) [Pubmed]
  4. AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Petersen, S., Casellas, R., Reina-San-Martin, B., Chen, H.T., Difilippantonio, M.J., Wilson, P.C., Hanitsch, L., Celeste, A., Muramatsu, M., Pilch, D.R., Redon, C., Ried, T., Bonner, W.M., Honjo, T., Nussenzweig, M.C., Nussenzweig, A. Nature (2001) [Pubmed]
  5. Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin-induced arrest. Hammond, E.M., Green, S.L., Giaccia, A.J. Mutat. Res. (2003) [Pubmed]
  6. Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. Alt, J.R., Bouska, A., Fernandez, M.R., Cerny, R.L., Xiao, H., Eischen, C.M. J. Biol. Chem. (2005) [Pubmed]
  7. Nibrin functions in Ig class-switch recombination. Kracker, S., Bergmann, Y., Demuth, I., Frappart, P.O., Hildebrand, G., Christine, R., Wang, Z.Q., Sperling, K., Digweed, M., Radbruch, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. An inducible null mutant murine model of Nijmegen breakage syndrome proves the essential function of NBS1 in chromosomal stability and cell viability. Demuth, I., Frappart, P.O., Hildebrand, G., Melchers, A., Lobitz, S., Stöckl, L., Varon, R., Herceg, Z., Sperling, K., Wang, Z.Q., Digweed, M. Hum. Mol. Genet. (2004) [Pubmed]
  9. Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome. Vissinga, C.S., Yeo, T.C., Woessner, J., Massa, H.F., Wilson, R.K., Trask, B.J., Concannon, P. Cytogenet. Cell Genet. (1999) [Pubmed]
  10. Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks. Yang, Y.G., Saidi, A., Frappart, P.O., Min, W., Barrucand, C., Dumon-Jones, V., Michelon, J., Herceg, Z., Wang, Z.Q. EMBO J. (2006) [Pubmed]
  11. Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models. Difilippantonio, S., Celeste, A., Fernandez-Capetillo, O., Chen, H.T., Reina San Martin, B., Van Laethem, F., Yang, Y.P., Petukhova, G.V., Eckhaus, M., Feigenbaum, L., Manova, K., Kruhlak, M., Camerini-Otero, R.D., Sharan, S., Nussenzweig, M., Nussenzweig, A. Nat. Cell Biol. (2005) [Pubmed]
  12. Cancer predisposition and hematopoietic failure in Rad50(S/S) mice. Bender, C.F., Sikes, M.L., Sullivan, R., Huye, L.E., Le Beau, M.M., Roth, D.B., Mirzoeva, O.K., Oltz, E.M., Petrini, J.H. Genes Dev. (2002) [Pubmed]
WikiGenes - Universities