Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation
- 1 June 2000
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 14 (11) , 1400-1406
- https://doi.org/10.1101/gad.14.11.1400
Abstract
Cancer-causing mutations often arise from gross chromosomal rearrangements (GCRs) such as translocations, which involve genetic exchange between nonhomologous chromosomes. Here we show that murineBrca2 has an essential function in suppressing GCR formation after chromosome breakage. Cells that harbor truncated Brca2spontaneously incur GCRs and genomic DNA breaks during division. They exhibit hypersensitivity to DNA damage by interstrand cross-linkers, which even at low doses trigger aberrant genetic exchange between nonhomologous chromosomes. Therefore, genetic instability in Brca2-deficient cells results from the mutagenic processing of spontaneous or induced DNA damage into gross chromosomal rearrangements, providing a mechanistic basis for cancer predisposition.Keywords
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