The project includes two parts: 1) Mutations in RecQ-helicase genes, BLM, WRN, and RECQ4 associate with autosomal recessive premature aging disorders. RecQ helicase deficient human cells have an increased level of DNA damage and/or telomere attrition. We are in the process to examine the role of RecQ helicases in telomere DNA damage repair and telomere length maintenance in human cells. In addition, we are screening for helicase-like proteins that associate with telomeres by dual-tag based affinity purification in combination with tandem mass spectrometry approach. 2) Fanconi anemia (FA) is an autosomal recessive disorder. FANCC is one of commonly mutated FA genes in FA patients and the FANCC subtype tends to associate with early onset of bone-marrow failure and hematologic malignancies. Prior reports showed telomere shortening in patients with Fanconi anemia. We have initiated the studies on the role of FANCC in telomere length maintenance in vivo. Our preliminary data suggest that FANCC may suppress telomere attrition, thus limiting hematopoietic cell death or immortalization. These studies will unveil potential novel mechanism(s) of how helicase and FA proteins may impact telomere integrity and thus age-related disease.