Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs, results in higher gene targeting efficiency

Juan Domínguez-Bendala, Mitsuko Masutani, Jim McWhir

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The viability of non-homologous end-joining (NHEJ)-defective mice suggests that homologous recombination (HR) might take over its role in DNA repair. To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PKcs, Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells. We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ. To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1. However, TF was not enhanced in Ku80- or DNA-PKcs-defective cells. Our study also suggests an unexpected involvement of DNA-PKcs in HR.

Original languageEnglish (US)
Pages (from-to)389-393
Number of pages5
JournalCell Biology International
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • DNA-PK
  • ES cells
  • Gene targeting
  • Homologous recombination
  • Ku80
  • PARP-1

ASJC Scopus subject areas

  • Cell Biology

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