期刊
EXPERIMENTAL GERONTOLOGY
卷 42, 期 9, 页码 871-878出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2007.04.011
关键词
aging; Werner syndrome; DNA repair; replication; telomere; base excision repair; recombination
资金
- Intramural NIH HHS Funding Source: Medline
Werner syndrome (WS) is an excellent model system for the study of human aging. WRN, a nuclear protein mutated in WS, plays multiple roles in DNA metabolism. Our understanding about the metabolic regulation and function of this RecQ helicase has advanced greatly during the past decade, largely due to the availability of purified WRN protein, WRN knockdown cells, and WRN knockout mice. Recent biochemical and genetic studies indicate that WRN plays significant roles in DNA replication, DNA repair, and telomere maintenance. Interestingly, many WRN functions require handling of DNA ends during S-phase, and evidence suggests that WRN plays both upstream and downstream roles in the response to DNA damage. Future research should focus on the mechanism(s) of WRN in the regulation of the various DNA metabolism pathways and development of therapeutic approaches to treat premature aging syndromes such as WS. Published by Elsevier Inc.
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