Phenotypic effects of heterozygosity for a BRCA2 mutation

Warren, Madhuri and Lord, Christopher J. and Masabanda, Julio S. and Griffin, Darren K. and Ashworth, Alan (2003) Phenotypic effects of heterozygosity for a BRCA2 mutation. Human Molecular Genetics, 12 (20). pp. 2645-2656. ISSN 0964-6906. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Heterozygous carriers of mutations in the BRCA2 gene have a high risk of developing breast and other cancers. In these individuals, BRCA2 appears to act as a tumour suppressor gene, in that loss of the wild type allele is frequently observed within tumours, leading to loss of BRCA2 function. Because BRCA2 functions in DNA repair via homologous recombination, this leads to genomic instability. However, it is unclear whether loss of the wild type allele is stochastic or if heterozygosity for BRCA2 mutation carries a phenotype that contributes to tumorigenic progression. Here we demonstrate that, in a specific vertebrate cell type, the chicken B cell line DT40, heterozygosity for a BRCA2 mutation has a distinct phenotype. This is characterized by a reduced growth rate, increased cell death, heightened sensitivity to specific DNA damaging agents and reduced RAD51 focus formation after irradiation. Thus in certain cell types, genome instability might be driven directly by heterozygosity for BRCA2 mutation.

Item Type: Article
Additional information: 12928478 0964-6906
Uncontrolled keywords: Alleles Animals Avian Proteins B-Lymphocytes BRCA2 Protein Cell Death Cell Division Cell Survival Chickens DNA Damage DNA-Binding Proteins Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Genome Heterozygote Humans In Situ Hybridization, Fluorescence Microscopy, Fluorescence Models, Genetic Mutation Phenotype Plasmids Rad51 Recombinase Recombination, Genetic Transfection
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Darren Griffin
Date Deposited: 12 Sep 2008 13:48
Last Modified: 14 Jul 2014 12:41
Resource URI: (The current URI for this page, for reference purposes)
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