NBN (Nijmegen breakage syndrome 1)
2002-10-01 Nancy Uhrhammer , Jacques-Olivier Bay , Richard A Gatti AffiliationCentre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
DNA/RNA
Description
spans over 51 kb; 16 exons
Transcription
4.4 and 2.6 kb (alternative polyadenylation); open reading frame of 2265 nucleotides
Proteins
Description
the 754 amino acid protein is called nibrin; predicted MW 85 kDa, 95 kDa by SDS-PAGE; contains in N-term a forkhead associated domain (amino acids 24-100) and a breast cancer domain (BRCT; amino acids 105-190), both domains being found in the various DNA damage responsive cell cycle checkpoint proteins; 4 possible nuclear localization domains in the C-term half. Identified as the p95 subunit of the Rad50/Mre11/p95 double-strand DNA break repair complex. Nibrin is an essential component of this complex, and is responsible for its nuclear localization.
Expression
wide; shorter transcript expressed at higher level in the testis (plays a role in DNA damage repair, though not in meiotic recombination, as ATM does)
Function
member of the MRE/RAD50/nibrin double-strand break repair complex of 1600 kDa; necessary for localization of Rad50/Mre11 at DSB sites, and for the nucleolytic activities of this complex. Mice homozygous for null alleles of Nbs1 are inviable, while those with mutations corresponding to the common human mutation recapitulate the NBS phenotype. A 70 kDa protein containing the C-terminal portion of NBS1 produced from an alternative initiation site is associates with Rad50 and Mre11 and is apparently partially functional.
Homology
no known homology
Mutations
Germinal
missense mutations in the BRCT domain or truncating mutations downstream the BRCT are found in Nijmegen breakage syndrome (see below); most mutations are a 5 base deletion at codon 218, called 657del5, and are due to a founder effect
Somatic
Missense mutations in NBS1 have been associated with childhood acute lymphoblastic leukemia.
Implicated in
Entity name
Disease
Nijmegen breakage syndrome is a chromosome instability syndrome/cancer prone disease at risk of non Hodgkin lymphomas
Cytogenetics
chromosome rearrangements involving immunoglobulin superfamilly genes, in particular inv(7)(p13q35)
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11438675 | 2001 | Chk2 activation dependence on Nbs1 after DNA damage. | Buscemi G et al |
| 9590181 | 1998 | The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. | Carney JP et al |
| 10391882 | 1999 | The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. | Dong Z et al |
| 9271379 | 1997 | Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. | Jongmans W et al |
| 9315668 | 1997 | hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks. | Maser RS et al |
| 11279524 | 2001 | An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. | Maser RS et al |
| 9620777 | 1998 | Positional cloning of the gene for Nijmegen breakage syndrome. | Matsuura S et al |
| 11325820 | 2001 | Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL). | Varon R et al |
| 9590180 | 1998 | Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. | Varon R et al |
| 11967151 | 2002 | A murine model of Nijmegen breakage syndrome. | Williams BR et al |
| 10426999 | 1999 | Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. | Zhong Q et al |
| 11756000 | 2001 | Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect. | van Engelen BG et al |
Other Information
Locus ID:
NCBI: 4683
MIM: 602667
HGNC: 7652
Ensembl: ENSG00000104320
Variants:
dbSNP: 4683
ClinVar: 4683
TCGA: ENSG00000104320
COSMIC: NBN
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38192153 | 2024 | Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer. | 0 |
| 38192153 | 2024 | Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer. | 0 |
| 36346689 | 2023 | NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects. | 3 |
| 36806726 | 2023 | The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation. | 0 |
| 37006067 | 2023 | XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population. | 1 |
| 37296499 | 2023 | Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas. | 1 |
| 36346689 | 2023 | NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects. | 3 |
| 36806726 | 2023 | The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation. | 0 |
| 37006067 | 2023 | XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population. | 1 |
| 37296499 | 2023 | Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas. | 1 |
| 34674288 | 2022 | Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis. | 4 |
| 35019694 | 2022 | Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n. | 4 |
| 35076389 | 2022 | Structure of the human ATM kinase and mechanism of Nbs1 binding. | 16 |
| 35164849 | 2022 | Association of DNA repair genes polymorphisms with childhood acute lymphoblastic leukemia: a high-resolution melting analysis. | 0 |
| 34674288 | 2022 | Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis. | 4 |
Citation
Nancy Uhrhammer ; Jacques-Olivier Bay ; Richard A Gatti
NBN (Nijmegen breakage syndrome 1)
Atlas Genet Cytogenet Oncol Haematol. 2002-10-01
Online version: http://atlasgeneticsoncology.org/gene/160/nbn-(nijmegen-breakage-syndrome-1)
Historical Card
1999-10-01 NBN (Nijmegen breakage syndrome 1) by Nancy Uhrhammer,Jacques-Olivier Bay,Richard A Gatti Affiliation
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
1998-11-01 NBN (Nijmegen breakage syndrome 1) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
