The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy
Authors:
Open Access
- 15 September 2014
- journal article
- review article
- Published by Springer Nature in Oncogene
- Vol. 34 (26) , 3349-3356
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.Keywords
This publication has 147 references indexed in Scilit:
- The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolaseNature, 2011
- The DNA Damage Response: Making It Safe to Play with KnivesMolecular Cell, 2010
- Regulation of DNA‐damage responses and cell‐cycle progression by the chromatin remodelling factor CHD4The EMBO Journal, 2010
- The DNA-damage response in human biology and diseaseNature, 2009
- Nbs1 Flexibly Tethers Ctp1 and Mre11-Rad50 to Coordinate DNA Double-Strand Break Processing and RepairCell, 2009
- 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage responseDNA Repair, 2009
- Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cellsCell Research, 2008
- DNA damage response as a candidate anti-cancer barrier in early human tumorigenesisNature, 2005
- The PARP superfamilyBioEssays, 2004
- Identification of a RING protein that can interact in vivo with the BRCA1 gene productNature Genetics, 1996