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 and chromosomal abnormalities, including 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. 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. 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 have now successfully purified a human RecQ4 complex and identified its associated components. These components are enzymes that can modify proteins postranslationally. We are currently investigating the function of this complex.
