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The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy
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Journal Article
The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Chromatin Assembly and Disassembly - drug effects
/ Chromatin Assembly and Disassembly - physiology
/ DNA
/ DNA Breaks, Double-Stranded - drug effects
/ Enzyme Inhibitors - pharmacology
/ Enzyme Inhibitors - therapeutic use
/ Enzymes
/ Humans
/ Medicine
/ Oncology
/ Poly Adenosine Diphosphate Ribose - metabolism
/ Poly(ADP-ribose) Polymerase Inhibitors
/ Poly(ADP-ribose) Polymerases - metabolism
/ Protein Processing, Post-Translational - drug effects
/ Protein Processing, Post-Translational - physiology
/ review
/ Ribose
/ Transcription Factors - metabolism
/ Tumors
