title: Werner syndrome protein positively regulates XRCC4-like factor transcription.
abstract: XRCC4-like factor (XLF) is involved in non-homologous end joining-mediated repair of DNA double-strand breaks (DSBs). Mutations in the WRN gene results in the development of Werner syndrome (WS), a rare autosomal recessive disorder characterized by premature ageing and genome instability. In the present study, it was identified that XLF protein levels were lower in WRN-deficient fibroblasts, compared with normal fibroblasts. Depletion of WRN in HeLa cells led to a decrease of XLF mRNA and its promoter activity. Chromatin immunoprecipitation assays demonstrated that WRN was associated with the XLF promoter. Depletion of XLF in normal human fibroblasts increased the percentage of β-galactosidase (β-gal) staining-positive cells, indicating acceleration in cellular senescence. Taken together, the results suggest that XLF is a transcriptional target of WRN and may be involved in the regulation of cellular senescence.
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P.R. China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Deng
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P.R. China.
authors.forename: Chongzhen
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, P.R. China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P.R. China.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D053484:RecQ Helicases / Q000378:metabolism*; D014158:Transcription, Genetic; D000071657:Werner Syndrome Helicase
chemical_list: D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D045643:DNA Repair Enzymes