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2009 | 56 | 2 |

Tytuł artykułu

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

Warianty tytułu

Języki publikacji

EN

Abstrakty

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.

Wydawca

-

Rocznik

Tom

56

Numer

2

Opis fizyczny

p.243-248,fig.,ref.

Twórcy

  • M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland

Bibliografia

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Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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