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 gammaH2AX 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 gammaH2AX 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.

journal_name

Acta Biochim Pol

journal_title

Acta biochimica Polonica

authors

Wojewódzka M,Kruszewski M,Buraczewska I,Xu W,Massuda E,Zhang J,Szumiel I

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

63-9

issue

1

eissn

0001-527X

issn

1734-154X

pii

20071374

journal_volume

54

pub_type

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