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

• DOI: 10.1074/jbc.c100035200
• Publication Date: 2002-07-26T15:09:24Z
• Authors: Yoh-ichi Kawabe; Dana Branzei; Tomoko Hayashi; Hirobumi Suzuki; Takashi Masuko; Fumitoshi Onoda; Seok-Jin Heo; Hideo Ikeda; Akira Shimamoto; Yasuhiro Furuichi; Masayuki Seki; Takemi Enomoto
• Keywords: 0301 basic medicine; Base Sequence; Sequence Homology, Amino Acid; Molecular Sequence Data; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; ATPases Associated with Diverse Cellular Activities; Humans; Amino Acid Sequence; Werner Syndrome; Carrier Proteins; DNA Primers; Protein Binding

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 Werner helicase 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 and sgs1 disruptants resulted in slightly accelerated aging and enhancement of the premature aging phenotype of sgs1 disruptants, respectively. In contrast, disruption of the yWHIP gene partially alleviated the sensitivity to methyl methanesulfonate of sgs1 disruptants.