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Oncogene. 2015 Jun;34(26):3349-56. doi: 10.1038/onc.2014.295. Epub 2014 Sep 15.

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

Author information

1
1] Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University Third Hospital, Beijing, China [2] Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
2
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

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.

PMID:
25220415
PMCID:
PMC4362780
DOI:
10.1038/onc.2014.295
[Indexed for MEDLINE]
Free PMC Article

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