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NBN (Nijmegen breakage syndrome 1)

Identity

Other namesNBS1 (Nijmegen breakage syndrome 1)
HGNC (Hugo) NBN
LocusID (NCBI) 4683
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

Nomenclature
HGNC (Hugo)NBN   7652
Cards
AtlasNBS1ID160
Entrez_Gene (NCBI)NBN  4683  nibrin
GeneCards (Weizmann)NBN
Ensembl (Hinxton)ENSG00000104320 [Gene_View]  chr8:90945564-90996899 [Contig_View]  NBN [Vega]
AceView (NCBI)NBN
Genatlas (Paris)NBN
WikiGenes4683
SOURCE (Princeton)NM_001024688 NM_002485
Genomic and cartography
GoldenPath (UCSC)NBN  -  8q21.3   chr8:90945564-90996899 -  8q21-q24   [Description]    (hg19-Feb_2009)
EnsemblNBN - 8q21-q24 [CytoView]
Mapping of homologs : NCBINBN [Mapview]
OMIM251260   602667   
Gene and transcription
Genbank (Entrez)AF051334 AF058696 AK001017 AK223256 AK289848
RefSeq transcript (Entrez)NM_001024688 NM_002485
RefSeq genomic (Entrez)AC_000140 NC_000008 NC_018919 NG_008860 NT_008046 NW_001839136 NW_004929340
Consensus coding sequences : CCDS (NCBI)NBN
Cluster EST : UnigeneHs.492208 [ NCBI ]
CGAP (NCI)Hs.492208
Alternative Splicing : Fast-db (Paris)GSHG0029703
Alternative Splicing GalleryENSG00000104320
Gene ExpressionNBN [ NCBI-GEO ]     NBN [ SEEK ]   NBN [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60934 (Uniprot)
NextProtO60934  [Medical]
With graphics : InterProO60934
Splice isoforms : SwissVarO60934 (Swissvar)
Domaine pattern : Prosite (Expaxy)BRCT (PS50172)    FHA_DOMAIN (PS50006)   
Domains : Interpro (EBI)BRCT_dom    DNA-repair_Nbs1_C    FHA_dom    Nibrin_met    SMAD_FHA_domain   
Related proteins : CluSTrO60934
Domain families : Pfam (Sanger)FHA (PF00498)    Nbs1_C (PF08599)   
Domain families : Pfam (NCBI)pfam00498    pfam08599   
Domain families : Smart (EMBL)BRCT (SM00292)  FHA (SM00240)  
DMDM Disease mutations4683
Blocks (Seattle)O60934
Human Protein AtlasENSG00000104320
Peptide AtlasO60934
HPRD04050
IPIIPI00299463   IPI01012909   IPI00974093   IPI00607775   IPI01013693   IPI00978422   
Protein Interaction databases
DIP (DOE-UCLA)O60934
IntAct (EBI)O60934
FunCoupENSG00000104320
BioGRIDNBN
InParanoidO60934
Interologous Interaction database O60934
IntegromeDBNBN
STRING (EMBL)NBN
Ontologies - Pathways
Ontology : AmiGODNA damage checkpoint  telomere maintenance  double-strand break repair via homologous recombination  nuclear chromosome, telomeric region  blastocyst growth  damaged DNA binding  ATP-dependent DNA helicase activity  protein binding  nucleus  nucleoplasm  replication fork  nucleolus  DNA repair  double-strand break repair  double-strand break repair  apoptotic process  cell cycle arrest  mitotic cell cycle checkpoint  mitotic G2 DNA damage checkpoint  meiosis  transcription factor binding  cell proliferation  PML body  regulation of DNA-dependent DNA replication initiation  DNA damage response, signal transduction by p53 class mediator  Mre11 complex  positive regulation of protein autophosphorylation  DNA duplex unwinding  positive regulation of kinase activity  site of double-strand break  nuclear inclusion body  isotype switching  protein N-terminus binding  neuromuscular process controlling balance  
Ontology : EGO-EBIDNA damage checkpoint  telomere maintenance  double-strand break repair via homologous recombination  nuclear chromosome, telomeric region  blastocyst growth  damaged DNA binding  ATP-dependent DNA helicase activity  protein binding  nucleus  nucleoplasm  replication fork  nucleolus  DNA repair  double-strand break repair  double-strand break repair  apoptotic process  cell cycle arrest  mitotic cell cycle checkpoint  mitotic G2 DNA damage checkpoint  meiosis  transcription factor binding  cell proliferation  PML body  regulation of DNA-dependent DNA replication initiation  DNA damage response, signal transduction by p53 class mediator  Mre11 complex  positive regulation of protein autophosphorylation  DNA duplex unwinding  positive regulation of kinase activity  site of double-strand break  nuclear inclusion body  isotype switching  protein N-terminus binding  neuromuscular process controlling balance  
Pathways : BIOCARTAATM Signaling Pathway [Genes]    Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes]   
Pathways : KEGGHomologous recombination   
REACTOMENBN
Protein Interaction DatabaseNBN
Wikipedia pathwaysNBN
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NBN
SNP (GeneSNP Utah)NBN
SNP : HGBaseNBN
Genetic variants : HAPMAPNBN
1000_GenomesNBN 
ICGC programENSG00000104320 
Somatic Mutations in Cancer : COSMICNBN 
CONAN: Copy Number AnalysisNBN 
Mutations and Diseases : HGMDNBN
OMIM251260    602667   
GENETestsNBN
Disease Genetic AssociationNBN
Huge Navigator NBN [HugePedia]  NBN [HugeCancerGEM]
Genomic VariantsNBN  NBN [DGVbeta]
Exome VariantNBN
dbVarNBN
ClinVarNBN
snp3D : Map Gene to Disease4683
General knowledge
Homologs : HomoloGeneNBN
Homology/Alignments : Family Browser (UCSC)NBN
Phylogenetic Trees/Animal Genes : TreeFamNBN
Chemical/Protein Interactions : CTD4683
Chemical/Pharm GKB GenePA31457
Clinical trialNBN
Cancer Resource (Charite)ENSG00000104320
Other databases
Probes
Litterature
PubMed344 Pubmed reference(s) in Entrez
CoreMineNBN
iHOPNBN

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 articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written11-1998Jean-Loup Huret
Updated10-1999Nancy Uhrhammer, Jacques-Olivier Bay and Richard A Gatti
Updated10-2002Nancy 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 .
Uhrhammer N, Bay JO and Gatti RA . NBN (Nijmegen breakage syndrome 1). Atlas Genet Cytogenet Oncol Haematol. October 1999 .
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

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37477/1/11-1998-NBS1ID160.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/2042/37551/1/10-1999-NBS1ID160.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/2042/37922/1/10-2002-NBS1ID160.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Mar 31 08:43:18 CEST 2014

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