Genetic analysis of BRCA1 function in a defined tumor cell line

Retrovirally expressed, wild-type BRCA1 decreased the gamma radiation (IR) sensitivity and increased the efficiency of double-strand DNA break repair (DSBR) of the BRCA1(-/-) human breast cancer line, HCC1937. It also reduced its susceptibility to DSB generation by IR. By contrast, multiple, clinica lly validated, missense mutant BRCA1 products were nonfunctional in these a ssays. These data constitute the basis for a BRCA1 functional assay and sug gest that efficient repair of double-strand DNA breaks is linked to BRCA1 t umor suppression function.