The Werner Syndrome (WS) is a rare human genetic disease with many features of premature aging. It has been considered by many researchers as a useful model for human aging studies. The gene that caused WS phenotype has recently been cloned and was named WRN. It encodes a protein homologous to RecQ family of helicases. Indeed, the recombinant WRN protein produced using baculovirus expression system contains a DNA helicase activity as well as an exonuclease activity. Interestingly, analysis of different WS patients suggests that some WRN mutations may impair the interactions between WRN and other proteins. This raised a possibility that WRN functions within a multisubunit protein complex in vivo. We investigated this possibility by using gel-filtration chromatography. Our data showed that WRN exists in a large protein complex of 2 MDa in human HeLa nuclear extract. In order to fully understand the mechanism of the WRN helicase, we believe that it is critical to purify the entire machine which the WRN is only a part of. The WRN-associated proteins within this machine may play key roles in the cellular process in which WRN participates. We have now successfully purified one such complex and identified all its subunits by microsequencing. Characterization of this complex will be crucial for our understanding of how WRN functions, as well as how mutations in WRN cause the premature aging phenotype in WS patients - Werner, RecQ, helicase, Aging
