A novel protein interacts with the Werner's syndrome gene product physically and functionally

Citation
Y. Kawabe et al., A novel protein interacts with the Werner's syndrome gene product physically and functionally, J BIOL CHEM, 276(23), 2001, pp. 20364-20369
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
23
Year of publication
2001
Pages
20364 - 20369
Database
ISI
SICI code
0021-9258(20010608)276:23<20364:ANPIWT>2.0.ZU;2-M
Abstract
Werner's syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging. The gene responsible for WS encodes a protein homologo us to Escherichia coli RecQ. Here we describe a novel Werner helicase inter acting protein (WHIP), which interacts with the N-terminal portion of Werne r protein (WRN), containing the exonuclease domain. WHIP, which shows homol ogy to replication factor C family proteins, is conserved from E. coli to h uman. Ectopically expressed WHIP and WRN co-localized in granular structure s in the nucleus. The functional relationship between WHIP and WRN was indi cated by genetic analysis of yeast cells. Disruptants of the SGS1 gene of S accharomyces cerevisiae, which is the WRN homologue in yeast, show an accel erated aging phenotype and high sensitivity to methyl methanesulfonate as c ompared 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, resp ectively. In contrast, disruption of the yWHIP gene partially alleviated th e sensitivity to methyl methanesulfonate of sgs1 disruptants.