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

• Autorzy: Wojewodzka M. , Kruszewski M. , Buraczewska I. , Xu W. , Massuda E. , Zhang J. , Szumiel I.
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

sirtuin; sirtuin inhibitor; mutant cell; silent information regulator yeast gene; enzyme; DNA repair; yeast gene; histone deacetylase; double strand break; X-irradiation; comet assay; DNA-dependent protein kinase; chromatin conformation

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2007
• Tom: 54
• Numer: 1
• Opis fizyczny: p.63-69,fig.,ref.

Twórcy

autor

Wojewodzka M.

• Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 warsaw, Poland

autor

Kruszewski M.

autor

Buraczewska I.

autor

Xu W.

autor

Massuda E.

autor

Zhang J.

autor

Szumiel I.

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