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Review
. 2011 Mar;70(3):52-5.

The Werner's Syndrome RecQ helicase/exonuclease at the nexus of cancer and aging

Stephen G Chun  1 , David S Shaeffer, Peter K Bryant-Greenwood
Affiliations
Review

The Werner's Syndrome RecQ helicase/exonuclease at the nexus of cancer and aging

Stephen G Chun et al. Hawaii Med J. 2011 Mar.

Abstract

Werner's Syndrome (WS) or adult-onset progeria is an autosomal recessive disorder of accelerated aging caused by mutations of the DNA RecQ helicase/exonuclease (WRN). WRN is an ATP-dependent helicase with 3' to 5' DNA exonuclease activity that regulates the replicative potential of dividing cells, and WRN loss-of-function mutations promote cellular senescence and neoplastic transformation. These molecular findings translate clinically into adult-onset progeria manifested by premature hair graying, dermal atrophy, cardiovascular disease, and cancer predilection along with a markedly reduced life expectancy. Recently, a patient with WS who developed pancreatic adenocarcinoma was identified in Honolulu suggesting a significant prevalence of loss-of-function WRN mutations in Hawaii's Japanese-American population. Based upon the indigenous Japanese WRN loss-of-function mutation heterozygote rate of 6 per 1,000, we speculate the possibility of approximately 1,200 heterozygotes in Hawaii. Our ongoing studies aim to evaluate Hawaii's true allelic prevalence of WRN loss-of-function mutations in the Japanese-American population, and the role of WRN silencing in sporadic cancers. In summary, WRN plays a nexus-like role in the complex interplay of cellular events that regulate aging, and analysis of WRN polymorphisms in Hawaii's population will generate novel insights to advance care for age-related pathologies.

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Figures

Figure 1
Figure 1
Functional domains of the the Werner's Syndrome WRN RecQ helicase/exonuclease. HRDC, helicase RNase D C-terminus domain; NLS, nuclear localization sequence; RQC, RecQ conserved domain; TAD, transactivation domain.
Figure 2
Figure 2
Patients with Werner's Syndrome classically develop pathologic aging and “bird-like facies” with onset during the 2nd decade of life. Images reproduced with permission from Chun, et al.: Gastrointest Cancer Res 4: xx-xx (in press); © 2011 by International Society of Gastrointestinal Oncology.
See this image and copyright information in PMC

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