Inhibition of poly(ADP-ribose) polymerase activity affects its subcellular localization and DNA strand break rejoining

• Authors: Nadezhda I Ryabokon , Artur Cieślar-Pobuda , Joanna Rzeszowska-Wolny
• Languages of publication: EN

Abstracts

EN

Poly(ADP-ribose) polymerase (PARP) plays a crucial role in DNA repair. Modulation of its activity by stimulation or inhibition is considered as a potentially important strategy in clinical practice, especially to sensitize tumor cells to chemo- and radiotherapy through inhibition of DNA repair. Here we studied the effect of the three PARP inhibitors, 5-iodo-6-amino-benzopyrone (INH2BP), 1,5-isoquinolinediol (1,5-dihydroxyisoquinolinediol (1,5-IQD) and 8-hydroxy-2-methylquinazolin-4-[3H]one (NU1025), and for two of them the efficiency in slowing the rejoining of DNA strand breaks induced by H2O2 was compared. Inhibition of PARP changed its intranuclear localization markedly; cells exposed to the inhibitor NU1025 showed a significant tendency to accumulate PARP in large foci, whereas in untreated cells its distribution was more uniform. The speed and efficiency of rejoining of H2O2-induced DNA strand breaks were lower in cells incubated with a PARP inhibitor, and the kinetics of rejoining were modulated in a different manner by each inhibitor. At a concentration of 100 µM the efficiency of the inhibitors could be ranked in the order NU1025 > IQD > INH2BP. The two first compounds were able to decrease the overall PARP activity below the level detected in control cells, while INH2BP showed up to 40% PARP activity after exposure to H2O2.

Keywords

EN

DNA strand break rejoining; efficiency of PARP inhibition; PARP foci; poly(ADP-ribose) polymerase (PARP); PARP inhibitors

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2009
• Volume: 56
• Issue: 2
• Pages: 243-248

Dates

published

2009

received

2008-12-16

revised

2009-03-24

accepted

2009-04-24

(unknown)

2009-04-30

Contributors

author

Nadezhda I Ryabokon

• Department of Experimental and Clinical Radiobiology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

author

Artur Cieślar-Pobuda

• Institute of Automation, Silesian University of Technology, Gliwice, Poland

author

Joanna Rzeszowska-Wolny

• Department of Experimental and Clinical Radiobiology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

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