title: Radiation enhances caspase 3 cleavage of Rad51 in BRCA2-defective cells.
abstract: 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.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Aurora, Colorado 80010-7163, USA.
authors.forename: Erika T
authors.initials: ET
authors.lastname: Brown
authors.forename: Cheryl
authors.initials: C
authors.lastname: Robinson-Benion
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Holt
mesh_terms: D024682:BRCA2 Protein / Q000172:deficiency* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000528:radiation effects*; D051135:Rad51 Recombinase / Q000378:metabolism*
chemical_list: D024682:BRCA2 Protein; D061945:Caspase Inhibitors; D011480:Protease Inhibitors; D004247:DNA; D051135:Rad51 Recombinase; D053148:Caspase 3