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Several human diseases are associated with an early aging process and an increase in age associated diseases and malignancies. The hallmark example is Werner syndrome, and a key feature of these conditions is prominent genomic instability. Insight into the basic mechanism of the pathology of the diseases helps us understand the processes of genome stability and how it is defective in aging and cancer. A group of the diseases is the recQ helicase family, conserved from bacteria to man, and these helicases are often called the guardians of the genome. A goal of this research is to identify their protein partners with a view to elucidate the pathways in which they are involved. So far, studies with Werner protein (WRN) leads us to speculate that it functions in DNA repair and at the telomere end. We are studying Werner functional protein interactions and cellular roles to better clarify the mechanisms by which it operates in DNA repair. Our working model is that WRN participates in base excision and in recombinational DNA repair pathways and that its function as a coordinator involves regulation of its catalytic activities by post-translational modifications.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]