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 W...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-06, Vol.276 (23), p.20364-20369
Main Authors: Kawabe, Yoh-ichi, Branzei, Dana, Hayashi, Tomoko, Suzuki, Hirobumi, Masuko, Takashi, Onoda, Fumitoshi, Heo, Seok-Jin, Ikeda, Hideo, Shimamoto, Akira, Furuichi, Yasuhiro, Seki, Masayuki, Enomoto, Takemi
Format: Article
Language:English
Subjects:
Amino Acid Sequence
ATPases Associated with Diverse Cellular Activities
Base Sequence
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
DNA Primers
DNA-Binding Proteins
Humans
Molecular Sequence Data
Protein Binding
Saccharomyces cerevisiae
Sequence Homology, Amino Acid
SGS1 gene
Werner Syndrome - genetics
Werner Syndrome - metabolism
Werner's syndrome
WHIP protein
WRN protein
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C100035200