Abstract
The BRCA2 tumour suppressor protein is involved in maintaining genetic stability through its role in homologous recombination (HR), where it mediates RAD51-dependent strand invasion. Here, we show that BRCA2-defective cells are not completely impaired in HR by strand invasion although the spontaneous HR rate is 10-fold lower than that in wild-type cells. Furthermore, a DNA double-strand break (DSB) triggers HR repair by strand invasion also in BRCA2-defective cells, but less efficiently. Thus, either the strand invasion pathway(s) in which BRCA2 operates is still operative in the absence of a functional BRCA2, albeit at a reduced frequency, or there is a separate pathway for strand invasion still functional in BRCA2-deficient cells. Consistent with the latter hypothesis, we show that HR events occurring in BRCA2-defective cells differ from HR events in wild-type cells. These data suggest that BRCA2-defective hamster cells are impaired in short tract gene conversion but maintain proficiency in sister chromatid exchange.
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Acknowledgements
We thank Malgorzata Zdzienicka and Maria Jasin for materials and Mark Meuth and members of the Helleday laboratory for help and valuable discussions. The Biological & Biotechnological Sciences Research Council, the Swedish Cancer Society, the Swedish Research Council, the Swedish Agency for Animal Welfare and Yorkshire Cancer Research supported this work financially. NSG has a scholarship from the Kerman University of Medical Science, Iran.
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Saleh-Gohari, N., Helleday, T. Strand invasion involving short tract gene conversion is specifically suppressed in BRCA2-deficient hamster cells. Oncogene 23, 9136–9141 (2004). https://doi.org/10.1038/sj.onc.1208178
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DOI: https://doi.org/10.1038/sj.onc.1208178
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