Werner syndrome protein: functions in the response to DNA damage and replication stress in S-phase.
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.
Cheng
Wen-Hsing
WH
Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Muftuoglu
Meltem
M
Bohr
Vilhelm A
VA
D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D004261:DNA Replication; D005090:Exodeoxyribonucleases; D006801:Humans; D007797:Laminin / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics* / Q000502:physiology; D016196:S Phase; D016615:Telomere / Q000648:ultrastructure; D014898:Werner Syndrome / Q000235:genetics* / Q000378:metabolism; D000071657:Werner Syndrome Helicase
D007797:Laminin; C084098:laminin A; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase