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NBN (Nijmegen breakage syndrome 1)

Written1998-11Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated1999-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France
Updated2002-10Nancy Uhrhammer, Jacques-Olivier Bay, Richard A Gatti
Centre Jean-Perrin, BP 392, 63000 Clermont-Ferrand, France

(Note : for Links provided by Atlas : click)

Identity

Other aliasNBS1 (Nijmegen breakage syndrome 1)
LocusID (NCBI) 4683
Atlas_Id 160
Location 8q21.3  [Link to chromosome band 8q21]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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

Note
  
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)
  

Bibliography

Chk2 activation dependence on Nbs1 after DNA damage.
Buscemi G, Savio C, Zannini L, Miccichè 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
 
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
 
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
 
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
 
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
 
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
 
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
 
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, Seemanov´ 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
 
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
 
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
 
Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect.
van Engelen BG, Hiel JA, Gabreëls FJ, van den Heuvel LP, van Gent DC, Weemaes CM
Human immunology. 2001 ; 62 (12) : 1324-1327.
PMID 11756000
 

Citation

This paper should be referenced as such :
Uhrhammer, N ; Bay, JO ; Gatti, RA
NBS1 (Nijmegen breakage syndrome 1)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):10-11.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NBS1ID160.html
History of this paper:
Huret, JL. NBS1 (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):13-14.
http://documents.irevues.inist.fr/bitstream/handle/2042/37477/11-1998-NBS1ID160.pdf
Uhrhammer, N ; Bay, JO ; Gatti, RA. NBS1 (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):175-176.
http://documents.irevues.inist.fr/bitstream/handle/2042/37551/10-1999-NBS1ID160.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Eye: Posterior uveal melanoma


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Nijmegen breakage syndrome


External links

Nomenclature
Cards
AtlasNBS1ID160.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4683
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:44:54 CEST 2018

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