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

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

doi:10.1074/jbc.c100035200

Abstract

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.

Highlights

Werner’s syndrome (WS)1 is a rare autosomal recessive disorder characterized by premature aging and an early onset of age-related diseases including arteriosclerosis, malignant neoplasms, melituria, and cataract [1]
To gain an insight into the cellular processes in which Werner protein (WRN) is involved, we tried to identify proteins that interact with WRN by a yeast two-hybrid screening using cDNA encoding the mouse WRN as bait
We have recently obtained results showing that mouse WRN (mWRN) is covalently attached to SUMO-1 [36]

Summary

Introduction

Werner’s syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging. WHIP, which shows homology to replication factor C family proteins, is conserved from E. coli to human. The functional relationship between WHIP and WRN was indicated by genetic analysis of yeast cells.

Results

Conclusion