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 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.
Kawabe Yi
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Branzei
D
D
Hayashi
T
T
Suzuki
H
H
Masuko
T
T
Onoda
F
F
Heo
S J
SJ
Ikeda
H
H
Shimamoto
A
A
Furuichi
Y
Y
Seki
M
M
Enomoto
T
T
D000074183:ATPases Associated with Diverse Cellular Activities; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C430237:WRNIP1 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities