Resveratrol modulates DNA double-strand break repair pathways in an ATM/ATR-p53- and -Nbs1-dependent manner

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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

Susanne Andrea Gatz1, Marlen Keimling, Cindy Baumann

  • 1Children's Hospital of the University of Ulm, Eythstrasse 24, D-89075 Ulm, Germany. susanne.gatz@uniklinik-ulm.de

Carcinogenesis
|January 5, 2008
PubMed

Insights

Resveratrol (RV) inhibits DNA repair pathways, including homologous recombination (HR) and non-homologous end joining (NHEJ). This natural compound

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Resveratrol (RV) is known to inhibit tumor development through cell cycle control and apoptosis.
  • Its effects on genomic stability, particularly DNA double-strand break (DSB) repair, remain unclear.

Purpose of the Study:

  • To investigate the impact of Resveratrol on DNA double-strand break (DSB) repair mechanisms, specifically homologous recombination (HR) and non-homologous end joining (NHEJ).
  • To elucidate the molecular pathways, including ATM, p53, and Nbs1, involved in Resveratrol's modulation of DNA repair.

Main Methods:

  • Utilized an enhanced green fluorescent protein (EGFP) and I-SceI-based assay system in lymphoblastoid cell lines (LCLs) treated with Resveratrol.
  • Employed isogenic cell lines (TK6, WTK1) differing in p53 status, patient-derived LCLs (ataxia telangiectasia, Nijmegen breakage syndrome), p53 knockdown, and ATM/ATR inhibitors (caffeine).

Main Results:

  • Resveratrol inhibits both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair pathways.
  • HR inhibition by RV is dependent on an ATM-p53 pathway.
  • Microhomology-mediated NHEJ inhibition by RV involves an ATM/ATR-Nbs1-dependent pathway.
  • RV's effects on DNA repair are independent of its known effects on cell growth and death.

Conclusions:

  • Resveratrol activates ATM and/or ATR kinases, leading to the inhibition of key DNA repair pathways.
  • The repression of error-prone recombination pathways by RV may contribute to its chemopreventive effects observed in animal models.
  • Understanding RV's impact on DNA repair provides insights into its potential as a chemopreventive agent.

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