The RecQ DNA helicase was first discovered in E.coli as a component in DNA recombination pathways. RecQ homologs were later identified in yeast, human and other eukaryotes, with at least 5 RecQ helicases in human. Three of them, WRN, BLM and RecQ4, are mutated in three different corresponding genetic disorders -- Werner (WS), Bloom (BS) and Rothmund Thomson Syndromes (RTS). All three diseases share the characteristics of genome instability and predisposition to cancer, but each disease also has its distinctive symptoms. WS patients exhibit several aging features, such as skin atrophy and early graying hair, and show a premature incidence of age-related conditions including atherosclerosis, osteoporosis, type II diabetes mellitus, malignant neoplasm and cataracts. Cells derived from these patients have a shorter life-span than those from normal individuals, and are more similar to cells from old people. The chromosomal abnormalities in WS include reciprocal chromosomal translocations, extensive genomic deletions, and telomere abnormalities. Bloom syndrome patients show retarded growth, sun sensitivity, immunodeficiency, and a predisposition to a wide variety of cancers. The genome instability in BS is characterized by an increased tendency of sister chromatid exchanges. RTS is a rare disease associated with skin and skeletal abnormalities and some features of premature aging. Trisomy 8 mosaicism has been found in some of the patients. The different phenotypes of the three diseases suggest that each human RecQ helicase may have a unique function that cannot be substituted by others. However, it is especially intriguing that both WS and RTS patients display various degrees of premature aging phenotypes and develop several age-related disorders. In yeast, mutations of the RecQ helicase homologue, sgs1, similarly result in genomic instability and shortening of life-span. Therefore, this family of helicases could be important in preventing aging, presumably because the maintenance of genome stability is required. Our group has successfully purified complexes that contain WRN and BLM helicases. We plan to use the same strategy to purify the compplex that containst hRecQ4, the helicase involved in RTS syndrome. So far, we have produced antibodies against the human RecQ4 helicase, and are trying to purify the complex containing RecQ4. Once the complex is purified, the study of its subunit composition and biochemical activity will follow the models that we have used for other cases
