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Updated: Oct 8, 2026

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
Ultraviolet irradiation induces BRCA2 protein depletion through a p53-independent and protein synthesis-dependent
1Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
It has been suggested that BRCA2, the protein product of the breast cancer susceptibility gene BRCA2, is involved in DNA damage repair. It is therefore likely that BRCA2 plays a role in a signaling pathway induced by DNA-damaging agents. To test this possibility, we examined the alteration of the BRCA2 protein level in human cell lines after UV irradiation. We found that UV irradiation down-regulated BRCA2 in a dose-dependent manner in all cell lines tested. The down-regulation of BRCA2 occurred soon (within 4 h) after UV treatment. Surprisingly, down-regulation of BRCA2 by UV does not require functional p53, which has been suggested to be required for the down-regulation of BRCA1 and BRCA2 mRNAs by DNA-damaging agents. Moreover, the proteosome- and calpain-mediated protein degradation pathways do not have an important role in the UV-induced BRCA2 depletion. However, blocking protein synthesis 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 can protect cells from UV-mediated cell death.
Insights
UV radiation down-regulates BRCA2 protein levels, impacting DNA damage repair. Increased BRCA2 expression enhances cellular resistance to UV-induced damage, highlighting its role in DNA damage signaling pathways.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The BRCA2 protein is implicated in DNA damage repair.
- BRCA2's role in DNA-damaging signaling pathways is under investigation.
Purpose of the Study:
- To investigate the alteration of BRCA2 protein levels following UV irradiation.
- To determine if BRCA2 expression influences cellular resistance to UV damage.
Main Methods:
- Human cell lines were exposed to varying doses of UV irradiation.
- BRCA2 protein levels were monitored post-irradiation.
- Cellular resistance to UV was assessed with ectopic BRCA2 expression.
Main Results:
- UV irradiation caused a dose-dependent down-regulation of BRCA2 protein levels within 4 hours.
- BRCA2 down-regulation by UV does not require functional p53.
- Blocking protein synthesis temporarily inhibited BRCA2 depletion.
- Ectopic BRCA2 expression increased cellular resistance to high-dose UV irradiation.
Conclusions:
- BRCA2 is involved in the DNA damage signaling pathway induced by UV radiation.
- BRCA2 expression confers protection against UV-mediated cell death.
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