IMR Press / FBL / Volume 11 / Issue 3 / DOI: 10.2741/1999

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Werner syndrome: molecular insights into the relationships between defective DNA metabolism, genomic instability, cancer and aging
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1 Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, Kentucky
Academic Editor:Guo-Min Li
Front. Biosci. (Landmark Ed) 2006, 11(3), 2657–2671; https://doi.org/10.2741/1999
Published: 1 September 2006
(This article belongs to the Special Issue DNA repair genes and human diseases)
Abstract

Werner syndrome is a segmental progeroid disease characterized by increased cancer and acceleration of specific age-related phenotypes, due to loss of a protein known as WRN. Extensive research over the last decade has revealed much about WRN biochemistry and the etiology of Werner syndrome. WRN possesses multiple DNA-dependent enzymatic activities (ATPase, helicase, exonuclease, and strand annealing) and interacts with factors having established roles in DNA metabolic pathways. Although the exact functions of WRN remain unclear, accumulating evidence points to roles in proper resolution of replication blockage and in telomere maintenance. If WRN function is lost (as exemplified in cells from Werner patients), problems with replication and DNA damage processing arise, probably resulting in an increased number or persistence of strand breaks. In turn, these events lead to chromosomal and telomeric abnormalities or activate checkpoints that bring about early senescence or increased apoptosis. Thus, elevated cancer incidence associated with Werner syndrome is due to increased chromosomal changes, while the accelerated aging characteristics probably stem from telomere dysfunction leading to accumulation of non-functional senescent cells or excessive apoptotic cell death over time. More research is needed to determine whether these specific DNA-dependent mechanisms contribute to development of aging characteristics in normal individuals.

Keywords
Werner syndrome
RecQ helicases
Genomic Instability
Telomeres
Senescence
Apoptosis
Cancer
Aging
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