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Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome

Item Type:Article
Title:Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome
Creators Name:Varon, R. and Vissinga, C. and Platzer, M. and Cerosaletti, K.M. and Chrzanowska, K.H. and Saar, K. and Beckmann, G. and Seemanova, E. and Cooper, P.R. and Nowak, N.J. and Stumm, M. and Weemaes, C.M.R. and Gatti, R.A. and Wilson, R.K. and Digweed, M. and Rosenthal, A. and Sperling, K. and Concannon, P. and Reis, A.
Abstract:Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Cells from NBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from ataxia telangiectasia. We describe the positional cloning of a gene encoding a novel protein, nibrin. It contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain. A truncating 5 bp deletion was identified in the majority of NBS patients, carrying a conserved marker haplotype. Five further truncating mutations were identified in patients with other distinct haplotypes. The domains found in nibrin and the NBS phenotype suggest that this disorder is caused by defective responses to DNA double-strand breaks.
Keywords:Amino Acid Sequence, Amino Acid Sequence Homology, Base Sequence, Cell Cycle Proteins, Chromosome Aberrations, Chromosome Breakage, Chromosome Disorders, Chromosome Mapping, DNA Damage, DNA Repair, DNA Sequence Analysis, Founder Effect, Linkage Disequilibrium, Messenger RNA, Microcephaly, Molecular Cloning, Molecular Sequence Data, Nuclear Proteins, Pair 8 Human Chromosomes, Recessive Genes, Sequence Deletion, Syndrome
Publisher:Cell Press
Page Range:467-476
Date:1 May 1998
Official Publication:https://doi.org/10.1016/S0092-8674(00)81174-5
PubMed:View item in PubMed

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