Cancer letters
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The BRCA2 protein is involved in the maintenance of genomic stability through its key role in homologous recombination repair of DNA double strand breaks. Biallelic inactivation of BRCA2 leads to a defect in DNA repair and is associated with a chromosomal instability phenotype. Recent studies on familial breast cancer clusters revealed chromosomal rearrangements and higher rates of sister chromatid exchanges also in heterozygous BRCA2 mutation carriers. ⋯ BRCA2+/- cells showed lower amounts of the full-length BRCA2 protein compared to BRCA2+/+ cells. The kinetics of gamma-H2AX protein level revealed distinct defects in DNA double strand break repair in the BRCA2+/- cells. These results are indicative of a haploinsufficiency phenotype in BRCA2+/- cells, suggesting that reduced amounts of functional BRCA2 protein in BRCA2+/- carriers are insufficient for an efficient repair of DNA double strand breaks, a condition that could contribute to the impairment of genomic stability.