December 2009

PARP and PARG Cooperation

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Heat map showing the similar expression profiles of the 485 commonly regulated PARP-1 and PARG genes.

Poly(ADP-ribose) polymerase 1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) regulate transcriptional activity by modifying target nuclear proteins with the addition and removal of ADP-ribose polymers, respectively. While the role of PARP-1 has been established, the exact function of PARG in the nucleus is less clear, although it’s assumed that PARP-1 and PARG have opposing functions in gene regulation. In this article, however, the authors show that this is not the case. Combining short hairpin RNA (shRNA) knockdown with microarray analysis in MCF-7 cells, they determined that these two enzymes often act in a similar, rather than antagonistic, manner. PARP-1 and PARG generally localized to similar target promoters, most notably in genes for stress response and metabolism, and, in about half of the genes tested, PARP-1 binding was dependent on PARG. In addition, studies using shRNA-resistant catalytic mutants revealed that enzymatic activity was not required in some target genes. So, rather than being opposing forces, PARP-1 and PARG may act cooperatively to maintain the proper levels of ADP ribosylation on target genes. 

Global Analysis of Transcriptional Regulation by Poly(ADP-ribose) Polymerase-1 and Poly(ADP-ribose) Glycohydrolase in MCF-7 Human Breast Cancer Cells

Kristine M. Frizzell, Matthew J. Gamble, Jhoanna G. Berrocal, Tong Zhang, Raga Krishnakumar, Yana Cen, Anthony A. Sauve and W. Lee Kraus

J. Biol. Chem., published online Oct. 7, 2009

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