BRE plays an essential role in preventing replicative and DNA damage-induced premature senescence
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AbstractThe BRE gene, alias BRCC45, produces a 44 kDa protein that is normally distributed in both cytoplasm and nucleus. In this study, we used adult fibroblasts isolated from wild-type (WT) and BRE knockout (BRE-/-) mice to investigate the functional role of BRE in DNA repair and cellular senescence. We compared WT with BRE-/- fibroblasts at different cell passages and observed that the mutant fibroblasts entered replicative senescence earlier than the WT fibroblasts. With the use of gamma irradiation to induce DNA damage in fibroblasts, the percentage of SA-beta-Gal(+) cells was significantly higher in BRE-/- fibroblasts compared with WT cells, suggesting that BRE is also associated with DNA damage-induced premature senescence. We also demonstrated that the gamma irradiation induced gamma-H2AX foci, a DNA damage marker, persisted significantly longer in BRE-/- fibroblasts than in WT fibroblasts, confirming that the DNA repair process is impaired in the absence of BRE. In addition, the BRCA1-A complex recruitment and homologous recombination (HR)-dependent DNA repair process upon DNA damage were impaired in BRE-/- fibroblasts. Taken together, our results demonstrate a role for BRE in both replicative senescence and DNA damage-induced premature senescence. This can be attributed to BRE being required for BRCA1-A complex-driven HR DNA repair.
All Author(s) ListShi WT, Tang MK, Yao Y, Tang CC, Chui YL, Lee KKH
Journal nameScientific Reports
Detailed descriptionTo ORKTS: doi:10.1038/srep23506
Year2016
Month3
Day22
Volume Number6
PublisherNATURE PUBLISHING GROUP
ISSN2045-2322
eISSN2045-2322
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences; Science & Technology - Other Topics

Last updated on 2020-25-11 at 00:31