Radiation enhances caspase 3 cleavage of rad51 in BRCA2-defective cells

Brown, E. T., Robinson-Benion, C. and Holt, J. T. Radiation Enhances Caspase 3 Cleavage of Rad51 in BRCA2-Defective Cells. Radiat. Res. 169, 595-601 (2008). After DNA damage, caspases cleave and activate proteins involved in cell death by apoptosis but also cleave and inactivate proteins implicated in DNA repair. Here we report a rapid onset of Rad51 cleavage by caspase 3 in BRCA2-defective mouse and human cells. This rapid cleavage was reduced markedly by transfer of full-length human BRCA2 into BRCA2-defective mouse or human cells, which also blocked the association of caspase 3 and Rad51 proteins. Overall caspase 3 activity was increased in BRCA2-defective cells, but the time course was much slower than that for Rad51. cleavage. We further showed that caspase 3 cleavage of Rad51 resulted in a functional decrease in Rad51 strand exchange activity and that inhibition of caspase 3 activity increased Rad51 protein levels and Rad51 foci. These findings indicate that BRCA2 inhibits Rad51. cleavage and subsequent apoptosis. (c) 2008 by Radiation Research Society.