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J. Biol. Chem., Vol. 276, Issue 23, 20364-20369, June 8, 2001

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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, and Takemi Enomoto

From the  Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan, ^§ AGENE Research Institute, 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan, and the ^¶ Center for Basic Research, Kitasato Institute, Shirokane 5-9-1, Minato-ku, Tokyo 108-8642, Japan

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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AB056151 and AB056152 for mouse and human WHIP, respectively.

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