WRN counteracts the NHEJ pathway upon camptothecin exposure

Makoto Otsuki, Masayuki Seki, Yoh ichi Kawabe, Eri Inoue, Yu Peng Dong, Takuya Abe, Genta Kato, Akari Yoshimura, Shusuke Tada, Takemi Enomoto

研究成果: Article査読

19 被引用数 (Scopus)


We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70-/-/WRN-/- and DNA-PKcs-/-/-/WRN-/- double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN-/- cells showed higher sensitivity than wild-type cells, whereas KU70-/- and DNA-PKcs-/-/- cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN-/- cells to CPT, rendering them as resistant to CPT treatment as KU70-/- and DNA-PKcs-/-/- cells. On the other hand, CPT sensitivity of BLM-/- cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.

ジャーナルBiochemical and biophysical research communications
出版ステータスPublished - 2007 4月 6

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


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