Strand invasion involving short tract gene conversion is specifically suppressed in BRCA2-deficient hamster cells.
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.
The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Nasrollah
N
Saleh-Gohari
Thomas
T
Helleday
D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics*; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D005785:Gene Conversion; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange
D024682:BRCA2 Protein