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.

journal_name

Radiat Res

journal_title

Radiation research

authors

Brown ET,Robinson-Benion C,Holt JT

doi

10.1667/RR1129.1

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

595-601

issue

5

eissn

0033-7587

issn

1938-5404

pii

RR1129

journal_volume

169

pub_type

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