Ultraviolet irradiation induces BRCA2 protein depletion through a p53-independent and protein synthesis-dependent pathway

It has been suggested that BRCA2 the protein product of the breast cancer s usceptibility gene BRCA2, is involved in DNA damage repair. It is therefore likely that BRCA2 plays a role in a signaling pathway induced by DNA-damag ing agents. To test this possibility, we examined the alteration of the BRC A2 protein level in human cell lines after UV irradiation. We found that W irradiation down-regulated BRCA2 in a dose-dependent manner in all cell lin es tested. The down-regulation of BRCA2 occurred soon (within 4 h) after UV treatment. Surprisingly, downregulation of BRCA2 by UV does not require fu nctional p53, which has been suggested to be required for the down-regulati on of BRCA1 and BRCA2 mRNAs by DNA-damaging agents. Moreover, the proteosom e-and calpain-mediated protein degradation pathways do not have an importan t role in the W-induced BRCA2 depletion, However, blocking protein synthesi s temporally inhibited the depletion of BRCA2 and BRCA1 in some cell lines. Ectopic expression of BRCA2 in cells increased resistance of cells to high -dose UV irradiation. These results demonstrate that BRCA2 is involved in a DNA-damaging signaling pathway induced by UV radiation and that expression of BRCA2 fan protect cells from UV-mediated cell death.