Transcriptional activation by the Werner syndrome gene product in yeast.

ABSTRACT

Werner syndrome (WS) is characterized by the premature occurrence of many age-related features. Before the cloning of the gene for WS (WRN), several reports suggested that transcriptional defects of genes may relate to the mechanisms of the occurrence of WS and natural aging. Because WRN, which encodes a helicase (WRN-H), has been cloned, we are attempting to clarify the mechanism of the transcriptional abnormalities found in WS cells, using WRN and WRN-H. In this article, we studied transcriptional activation of a promoter by WRN-H in a yeast assay system as a first step. The results showed that WRN-H functions as a transcriptional activator in the system. Furthermore, we performed additional transcriptional assays using various parts of WRN to define the critical region of WRN-H for transcriptional activation in yeast. The results revealed the critical region for the activation most likely mapped to the region of 315 to 403 aa. The region of 404 to 1309 aa may also effect activation in the presence of the critical region. The two regions contain an acidic domain, and the region of 404 to 1309 aa also contains a helicase domain. If this transcriptional activation by WRN-H occurs also in human cells in vivo, direct activation of the promoters by WRN-H could explain the results of somatic cell hybrid studies as well as the overexpressed genes detected in WS cells. However, our results should be interpreted with caution, because thus far, the transcriptional activation by WRN-H were only demonstrated using one promoter in a yeast system.