| Identity |
| Other names | NBS1 (Nijmegen breakage syndrome 1) |
| HGNC (Hugo) | NBN |
| Location | 8q21.3 |
| Location_base_pair | Starts at 90945564 and ends at 90996899 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Note | see also, in Deep Insight section: Ataxia-Telangiectasia and variants |
| DNA/RNA |
| Description | spans over 51 kb; 16 exons |
| Transcription | 4.4 and 2.6 kb (alternative polyadenylation); open reading frame of 2265 nucleotides |
| Protein |
| 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 | Nijmegen breakage syndrome |
| 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) |
| External links |
| Bibliography |
| Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. |
| Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J |
| Molecular and cellular biology. 1997 ; 17 (9) : 5016-5022. |
| PMID 9271379 |
| hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks. |
| Maser RS, Monsen KJ, Nelms BE, Petrini JH |
| Molecular and cellular biology. 1997 ; 17 (10) : 6087-6096. |
| PMID 9315668 |
| The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. |
| Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH |
| Cell. 1998 ; 93 (3) : 477-486. |
| PMID 9590181 |
| Positional cloning of the gene for Nijmegen breakage syndrome. |
| Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, Smeets D, Solder B, Belohradsky BH, Der Kaloustian VM, Oshimura M, Isomura M, Nakamura Y, Komatsu K |
| Nature genetics. 1998 ; 19 (2) : 179-181. |
| PMID 9620777 |
| Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. |
| Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanovˆ° E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A |
| Cell. 1998 ; 93 (3) : 467-476. |
| PMID 9590180 |
| The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. |
| Dong Z, Zhong Q, Chen PL |
| The Journal of biological chemistry. 1999 ; 274 (28) : 19513-19516. |
| PMID 10391882 |
| Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. |
| Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH |
| Science (New York, N.Y.). 1999 ; 285 (5428) : 747-750. |
| PMID 10426999 |
| Chk2 activation dependence on Nbs1 after DNA damage. |
| Buscemi G, Savio C, Zannini L, Miccichˆ® F, Masnada D, Nakanishi M, Tauchi H, Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, Delia D |
| Molecular and cellular biology. 2001 ; 21 (15) : 5214-5222. |
| PMID 11438675 |
| An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. |
| Maser RS, Zinkel R, Petrini JH |
| Nature genetics. 2001 ; 27 (4) : 417-421. |
| PMID 11279524 |
| Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect. |
| van Engelen BG, Hiel JA, Gabreˆ´ls FJ, van den Heuvel LP, van Gent DC, Weemaes CM |
| Human immunology. 2001 ; 62 (12) : 1324-1327. |
| PMID 11756000 |
| Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL). |
| Varon R, Reis A, Henze G, von Einsiedel HG, Sperling K, Seeger K |
| Cancer research. 2001 ; 61 (9) : 3570-3572. |
| PMID 11325820 |
| A murine model of Nijmegen breakage syndrome. |
| Williams BR, Mirzoeva OK, Morgan WF, Lin J, Dunnick W, Petrini JH |
| Current biology : CB. 2002 ; 12 (8) : 648-653. |
| PMID 11967151 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 11-1998 | Jean-Loup Huret |
| Updated | 10-1999 | Nancy Uhrhammer, Jacques-Olivier Bay and Richard A Gatti |
| Updated | 10-2002 | Nancy Uhrhammer, Jacques-Olivier Bay and Richard A Gatti |
| Citation |
| This paper should be referenced as such : |
| Huret JL . NBN (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. November 1998 . URL : http://AtlasGeneticsOncology.org/Genes/NBS1ID160.html |
| Uhrhammer N, Bay JO and Gatti RA . NBN (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. October 1999 . URL : http://AtlasGeneticsOncology.org/Genes/NBS1ID160.html |
| Uhrhammer N, Bay JO and Gatti RA . NBN (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. October 2002 . URL : http://AtlasGeneticsOncology.org/Genes/NBS1ID160.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Jul 15 14:41:51 CEST 2010 |
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