A Novel Protein Interacts with the Werner's Syndrome Gene Product Physically and Functionally

Werner's syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging. The gene responsible for WS encodes a protein homologous to Escherichia coli RecQ. Here we describe a novel Wernerhelicase interacting protein (WHIP), which interacts with the N-terminal portion of Werner protein (WRN), containing the exonuclease domain. WHIP, which shows homology to replication factor C family proteins, is conserved from E. coli to human. Ectopically expressed WHIP and WRN co-localized in granular structures in the nucleus. The functional relationship between WHIP and WRN was indicated by genetic analysis of yeast cells. Disruptants of the SGS1 gene of Saccharomyces cerevisiae, which is the WRN homologue in yeast, show an accelerated aging phenotype and high sensitivity to methyl methanesulfonate as compared with wild-type cells. Disruption of the yeast WHIP(yWHIP) gene in wild-type cells andsgs1 disruptants resulted in slightly accelerated aging and enhancement of the premature aging phenotype of sgs1disruptants, respectively. In contrast, disruption of theyWHIP gene partially alleviated the sensitivity to methyl methanesulfonate of sgs1 disruptants.