Identification Of A Complex Involved In Werner Syndrome

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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 involved in WS 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 a 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 the possibility that WRN functions within a multisubunit protein complex in vivo. We have successfully purified one such complex and identified all its subunits by microsequencing. We found that this complex contains DNA-PKcs, Ku86, and Ku70 proteins. All these WRNp partners have previously been shown to participate in repair of DNA damage and in signaling pathways leading to cell cycle arrest and cell death. Our results are consistent with several publications from other groups which also found the interaction between WRNp and these proteins. Recently, we have used a different WRNp antibody and isolated a different form of the WRN complex, This new complex contains not only the DNA-PKcs, but also several novel proteins. One of them appears to be an interacting protein for lamin. One form of lamin, lamin-A, has been found to be defective in Hutchinson-Gilford progeria. We are speculating that this interacting protein may play a common role in premature aging from both diseases, and are currently investigating this connection.