Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks

Maria Wojewódzka, Marcin Kruszewski, Iwona Buraczewska, Weizheng Xu, Edmond Massuda, Jie Zhang, Irena Szumiel

Research output: Contribution to journalArticlepeer-review

Abstract

Sirtuins (type III histone deacetylases) are an important member of a group of enzymes that modify chromatin conformation. We investigated the role of sirtuin inhibitor, GPI 19015, in double strand break (DSB) repair in CHO-K1 wt and xrs-6 mutant cells. The latter is defective in DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end-joining (D-NHEJ). DSB were estimated by the neutral comet assay and histone γH2AX foci formation. We observed a weaker effect of GPI 19015 treatment on the repair kinetics in CHO wt cells than in xrs6. In the latter cells the increase in DNA repair rate was most pronounced in G1 phase and practically absent in S and G2 cell cycle phases. The decrease in the number of histone γH2AX foci was faster in xrs6 than in CHO-K1 cells. The altered repair rate did not affect survival of X-irradiated cells. Since in G1 xrs6 cells DNA-PK-dependent non-homologous end-joining, D-NHEJ, does not operate, these results indicate that inhibition of sirtuins modulates DNA-PK-independent (backup) non-homologous end-joining, B-NHEJ, to a greater extent than the other DSB repair system, D-NHEJ.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalActa Biochimica Polonica
Volume54
Issue number1
StatePublished - 2007
Externally publishedYes

Keywords

  • Comet assay
  • DNA-PK
  • DSB
  • GPI
  • Histone H2AX
  • NHEJ
  • X-irradiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Fingerprint Dive into the research topics of 'Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks'. Together they form a unique fingerprint.

Cite this