Telomere attrition in premature aging syndromes

National Institute On Aging

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Abstract

In humans, RecQ-helicase proteins include RECQ1, BLM, WRN, RECQ4 and RECQ5. Mutations in BLM, WRN, and RECQ4 associate with autosomal recessive premature aging disorders, Bloom syndrome (BS), Werner syndrome (WS), and Rothmund Thomson syndrome (RTS), characterized by genomic instability and cancer predisposition, respectively. Cells with defects in WRN or RECQ4 have an increased level of oxidative DNA base damage or increased sensitivities to oxidative stress. We propose to examine: (1) if oxidative DNA base damage accumulates in telomeres in WRN- and REQ4- deficient cells under oxidative stress, and if these DNA lesions affect telomere length and/or function; (2) if oxidative base damage affects telomere maintenance in other RecQ-deficient cells, e.g. RECQ1 and RECQ5; and (3) if RecQ-helicase proteins play a common role in oxidative DNA damage repair at telomeres. These studies will unveil potential novel mechanism(s) of how oxidative base lesions and RecQ-helicase proteins may impact telomere integrity and age-related disease.