PARP1 gene expression is downregulated by knockdown of PARG gene

Uchiumi,Fumiaki; Watanabe,Takeshi; Ohta,Ryo; Abe,Hideaki; Tanuma,Sei-Ichi

doi:10.3892/or.2013.2321

PARP1 gene expression is downregulated by knockdown of PARG gene

Authors:
- Fumiaki Uchiumi
- Takeshi Watanabe
- Ryo Ohta
- Hideaki Abe
- Sei-Ichi Tanuma
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Affiliations: Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan
Published online on: March 4, 2013 https://doi.org/10.3892/or.2013.2321
Pages: 1683-1688
Copyright: © Uchiumi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Poly(ADP-ribosyl)ation is a modification of nuclear proteins that regulates DNA replication, repair and transcription. In order to investigate the biological effects of degradation of poly(ADP-ribose), knockdown of the poly(ADP-ribose) glycohydrolase (PARG) gene was performed by introducing a short interfering RNA (siRNA)-pool into HeLa S3 cells. Notably, poly(ADP-ribosyl)ated proteins did not accumulate in the cells. Western blotting, quantitative RT-PCR analysis and a transient transfection assay revealed that poly(ADP-ribose) polymerase 1 (PARP1) gene/protein expression and its promoter activity were reduced in the PARG knockdown cells. These results suggest that the amount of poly(ADP-ribose) in a cell is regulated under the control of PARP1/PARG gene expression balance. Furthermore, in this study, we showed that PARG-siRNA enhanced cell death induced by staurosporine (STS). Thus, we propose a PARG-siRNA utilizing gene-therapy for cancer treatment.

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