2012 journal article
Differential effects of poly(ADP-ribose) polymerase inhibition on DNA break repair in human cells are revealed with Epstein-Barr virus
Proceedings of the National Academy of Sciences, 109(17), 6590–6595.
author keywords: base excision repair; BRCA
MeSH headings : Blotting, Western; Cell Cycle; DNA Damage; DNA Repair; Enzyme Inhibitors / pharmacology; Herpesvirus 4, Human / physiology; Humans; Infrared Rays; Plasmids / physiology; Poly(ADP-ribose) Polymerase Inhibitors; Polymerase Chain Reaction; Tumor Suppressor Protein p53 / physiology
TL;DR:
An in vivo repair assay based on large endogenous Epstein–Barr virus (EBV) circular episomes assessed quantitatively and simultaneously the induction and repair of SSBs and DSBs in human cells and demonstrated that the PARP1 protein was not essential for SSB repair.
(via Semantic Scholar)
open access via www.pnas.org (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(OpenAlex)
Source: Crossref
Added: September 28, 2019
Poly(ADP-ribose) polymerase (PARP) inhibitors can generate synthetic lethality in cancer cells defective in homologous recombination. However, the mechanism(s) by which they affect DNA repair has not been established. Here we directly determined the effects of PARP inhibition and PARP1 depletion on the repair of ionizing radiation-induced single- and double-strand breaks (SSBs and DSBs) in human lymphoid cell lines. To do this, we developed an in vivo repair assay based on large endogenous Epstein–Barr virus (EBV) circular episomes. The EBV break assay provides the opportunity to assess quantitatively and simultaneously the induction and repair of SSBs and DSBs in human cells. Repair was efficient in G1 and G2 cells and was not dependent on functional p53. shRNA-mediated knockdown of PARP1 demonstrated that the PARP1 protein was not essential for SSB repair. Among 10 widely used PARP inhibitors, none affected DSB repair, although an inhibitor of DNA-dependent protein kinase was highly effective at reducing DSB repair. Only Olaparib and Iniparib, which are in clinical cancer therapy trials, as well as 4-AN inhibited SSB repair. However, a decrease in PARP1 expression reversed the ability of Iniparib to reduce SSB repair. Because Iniparib disrupts PARP1–DNA binding, the mechanism of inhibition does not appear to involve trapping PARP at SSBs.