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 journalArticle

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

Fingerprint

DNA End-Joining Repair
DNA-Activated Protein Kinase
Joining
Repair
Sirtuins
CHO Cells
DNA
DNA Repair
Histones
Histone Deacetylases
Comet Assay
Cells
G1 Phase
Chromatin
Cell Cycle
Conformations
Assays
Enzymes
Kinetics

Keywords

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

ASJC Scopus subject areas

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

Cite this

Wojewódzka, M., Kruszewski, M., Buraczewska, I., Xu, W., Massuda, E., Zhang, J., & Szumiel, I. (2007). Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks. Acta Biochimica Polonica, 54(1), 63-69.

Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks. / Wojewódzka, Maria; Kruszewski, Marcin; Buraczewska, Iwona; Xu, Weizheng; Massuda, Edmond; Zhang, Jie; Szumiel, Irena.

In: Acta Biochimica Polonica, Vol. 54, No. 1, 2007, p. 63-69.

Research output: Contribution to journalArticle

Wojewódzka, M, Kruszewski, M, Buraczewska, I, Xu, W, Massuda, E, Zhang, J & Szumiel, I 2007, 'Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks', Acta Biochimica Polonica, vol. 54, no. 1, pp. 63-69.
Wojewódzka M, Kruszewski M, Buraczewska I, Xu W, Massuda E, Zhang J et al. Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks. Acta Biochimica Polonica. 2007;54(1):63-69.
Wojewódzka, Maria ; Kruszewski, Marcin ; Buraczewska, Iwona ; Xu, Weizheng ; Massuda, Edmond ; Zhang, Jie ; Szumiel, Irena. / Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks. In: Acta Biochimica Polonica. 2007 ; Vol. 54, No. 1. pp. 63-69.
@article{f679ddc1a4de48b8801244a16d1370d4,
title = "Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks",
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.",
keywords = "Comet assay, DNA-PK, DSB, GPI, Histone H2AX, NHEJ, X-irradiation",
author = "Maria Wojew{\'o}dzka and Marcin Kruszewski and Iwona Buraczewska and Weizheng Xu and Edmond Massuda and Jie Zhang and Irena Szumiel",
year = "2007",
language = "English (US)",
volume = "54",
pages = "63--69",
journal = "Acta Biochimica Polonica",
issn = "0001-527X",
publisher = "Acta Biochimica Polonica",
number = "1",

}

TY - JOUR

T1 - Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks

AU - Wojewódzka, Maria

AU - Kruszewski, Marcin

AU - Buraczewska, Iwona

AU - Xu, Weizheng

AU - Massuda, Edmond

AU - Zhang, Jie

AU - Szumiel, Irena

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - Comet assay

KW - DNA-PK

KW - DSB

KW - GPI

KW - Histone H2AX

KW - NHEJ

KW - X-irradiation

UR - http://www.scopus.com/inward/record.url?scp=33947587267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947587267&partnerID=8YFLogxK

M3 - Article

C2 - 17311110

AN - SCOPUS:33947587267

VL - 54

SP - 63

EP - 69

JO - Acta Biochimica Polonica

JF - Acta Biochimica Polonica

SN - 0001-527X

IS - 1

ER -