EVALUATING PARP1 DOMAINS AS GOSSYPOL TARGETS
Abstract
Poly ADP-ribose polymerase 1 (PARP1) is an important enzyme, which is involved in DNA repair, replication, and transcription. Prospective anti-cancer drug gossypol inhibits human PARP1, but the mechanism of inhibition remains unknown. Previously it has been shown that gossypol interacts with purified BRCA1 C-terminus (BRCT) domain in vitro, but it remains unclear whether it inhibits PARP1 through BRCT domain in the context of the full length protein. Here it is shown that the BRCT domain within the full-length PARP1 protein is not required for inhibition of catalytic activity of PARP1 by gossypol. Our data obtained using a series of PARP1 mutations and H4-dependent pathway of PARP1 activation also show that Zinc fingers, the DNA binding domains of PARP1, are not involved in the inhibition of PARP1 catalytic activity by gossypol. Thus the likely candidate target(s) for gossypol action are other domains of PARP1 or interdomain linkers.
About the Authors
S. Gross
Fox Chase Cancer Center, Philadelphia,
United States
Cancer Epigenetics Team
United States
Cancer Epigenetics Team
E. Yu. Kotova
Fox Chase Cancer Center, Philadelphia
United States
Cancer Epigenetics Team
United States
Cancer Epigenetics Team
N. V. Maluchenko
Lomonosov Moscow State University, Moscow
Russian Federation
Department of Bioengineering, School of Biology
Russian Federation
Department of Bioengineering, School of Biology
J. M. Pascal
Université de Montréal
Canada
Department of Biochemistry and Molecular Medicine
Canada
Department of Biochemistry and Molecular Medicine
V. M. Studitsky
Fox Chase Cancer Center, Philadelphia;
Moscow State University, Moscow
Russian Federation
Department of Bioengineering, School of Biolog, MSU
Russian Federation
Department of Bioengineering, School of Biolog, MSU
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Review
For citations:
Gross S., Kotova E.Yu., Maluchenko N.V., Pascal J.M., Studitsky V.M. EVALUATING PARP1 DOMAINS AS GOSSYPOL TARGETS. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2016;(4):61-65. (In Russ.)
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