Human Werner helicase interacting protein 1 (WRNIP1) functions as novel modulator for DNA polymerase δ

Toshiki Tsurimoto, Ayako Shinozaki, Masaki Yano, Masayuki Seki, Takemi Enomoto

研究成果: Contribution to journalArticle査読

51 被引用数 (Scopus)

抄録

Human WRNIP1, a Werner DNA helicase interacting protein 1, was expressed in insect cells and E. coli. The purified protein behaved as a homo-oligomeric complex with a native molecular mass indicative of an octamer, and the complex copurified with an ATPase activity that was stimulated by double-stranded DNA ends. As suggested by genetic studies of budding yeast WRNIP1/Mgs1, the purified human WRNIP1 complex interacted physically with human DNA polymerase δ (pol δ), stimulating its DNA synthesis activity more than fivefold in the presence or absence of proliferating cell nuclear antigen. Analysis of reaction products demonstrated the stimulation to be partly due to an increased processivity of pol δ but more importantly to an increase in its initiation frequency. Addition of ATP to reactions partially suppressed stimulation by WRNIP1. Furthermore, a mutant WRNIP1 lacking ATPase activity could stimulate pol δ normally but was insensitive to suppression by ATP. These results indicate that WRNIP1 functions as a modulator for initiation or restart events during pol δ-mediated DNA synthesis and that its ATPase activity is utilized to sense DNA ends and to regulate the extent of stimulation.

本文言語英語
ページ(範囲)13-22
ページ数10
ジャーナルGenes to Cells
10
1
DOI
出版ステータス出版済み - 1 2005

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 細胞生物学

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