WRN at telomeres: implications for aging and cancer.
Werner Syndrome (WS) is a premature aging syndrome characterized by early onset of age-related pathologies and cancer. Since WS is due to a single gene defect, it has attracted much interest from researchers seeking to understand pathways that contribute to cancer and aging at cellular and molecular levels. The protein mutated in WS, WRN, appears to play a major role in genome stability, particularly during DNA replication and telomere metabolism. Much of the pathophysiology associated with WS, including the rapid onset of cellular senescence, early cancer onset and premature aging, can be attributed to a defect in telomere maintenance. Recent genetic evidence from the mTerc(-/-) Wrn(-/-) mouse demonstrates that mice with critically shortened telomeres display aging phenotypes reminiscent of human WS, further reinforcing the notion that telomere dysfunction is required for the manifestation of aging pathophysiologies in the setting of WRN deficiency.
Multani
Asha S
AS
Department of Molecular Genetics, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Chang
Sandy
S
D000375:Aging / Q000502:physiology; D000818:Animals; D005090:Exodeoxyribonucleases; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D053484:RecQ Helicases / Q000235:genetics*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014898:Werner Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000071657:Werner Syndrome Helicase
D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C499253:Wrn protein, mouse