title: BRE plays an essential role in preventing replicative and DNA damage-induced premature senescence.
abstract: The 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-β-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 γ-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.
authors.affiliation: Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Shi
authors.affiliation: Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Mei Kuen
authors.initials: MK
authors.lastname: Tang
authors.affiliation: Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Chemical Pathology, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yiu Loon
authors.initials: YL
authors.lastname: Chui
authors.affiliation: Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Kenneth Ka Ho
authors.initials: KKH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence; D004249:DNA Damage; D004261:DNA Replication; D019398:Genes, BRCA1; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*
chemical_list: C484261:Babam2 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins