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The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy

Oncogene volume 34, pages 3349–3356 (2015)Cite this article

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Abstract

DNA damage is a deleterious threat, but occurs daily in all types of cells. In response to DNA damage, poly(ADP-ribosyl)ation, a unique post-translational modification, is immediately catalyzed by poly(ADP-ribose) polymerases (PARPs) at DNA lesions, which facilitates DNA damage repair. Recent studies suggest that poly(ADP-ribosyl)ation is one of the first steps of cellular DNA damage response and governs early DNA damage response pathways. Suppression of DNA damage-induced poly(ADP-ribosyl)ation by PARP inhibitors impairs early DNA damage response events. Moreover, PARP inhibitors are emerging as anti-cancer drugs in phase III clinical trials for BRCA-deficient tumors. In this review, we discuss recent findings on poly(ADP-ribosyl)ation in DNA damage response as well as the molecular mechanism by which PARP inhibitors selectively kill tumor cells with BRCA mutations.

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Acknowledgements

We thank Dr Chao Liu to proofread the manuscript. This work was supported by the National Institute of Health (CA132755 and CA130899 to XY). XY is a recipient of the Era of Hope Scholar Award from the Department of Defense. ML is a recipient of the Ovarian Cancer Research Foundation Award.

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  1. Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing, China

    M Li

  2. Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

    M Li & X Yu

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  2. X Yu
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Li, M., Yu, X. The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy. Oncogene 34, 3349–3356 (2015). https://doi.org/10.1038/onc.2014.295

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