Werner syndrome protein positively regulates XRCC4-like factor transcription

Liu,Dongyun; Deng,Xiaoli; Yuan,Chongzhen; Chen,Lin; Cong,Yusheng; Xu,Xingzhi

doi:10.3892/mmr.2014.2030

Werner syndrome protein positively regulates XRCC4-like factor transcription

Authors:
- Dongyun Liu
- Xiaoli Deng
- Chongzhen Yuan
- Lin Chen
- Yusheng Cong
- Xingzhi Xu
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Affiliations: Beijing Key Laboratory of DNA Damage Response, College of Life Science, Capital Normal University, Beijing 100048, P.R. China, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 310036, P.R. China
Published online on: March 10, 2014 https://doi.org/10.3892/mmr.2014.2030
Pages: 1648-1652
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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