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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Chromatin Assembly and Disassembly / drug effects
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Chromatin Assembly and Disassembly / physiology
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DNA Breaks, Double-Stranded / drug effects
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DNA Damage / drug effects
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DNA Damage / physiology*
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Humans
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Neoplasms / metabolism
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Poly Adenosine Diphosphate Ribose / metabolism*
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Poly(ADP-ribose) Polymerase Inhibitors
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Poly(ADP-ribose) Polymerases / metabolism*
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Protein Processing, Post-Translational / drug effects
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Protein Processing, Post-Translational / physiology*
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Transcription Factors / metabolism
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Poly(ADP-ribose) Polymerase Inhibitors
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Transcription Factors
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Poly Adenosine Diphosphate Ribose
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Poly(ADP-ribose) Polymerases