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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)477-482
Number of pages6
JournalBiochemical and biophysical research communications
Volume355
Issue number2
DOIs
Publication statusPublished - 2007 Apr 6

Keywords

  • BLM
  • CPT
  • DNA-PKcs
  • DT40
  • Etoposide
  • Ku70
  • PARP-1
  • RecQ
  • TopI
  • WRN

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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