Skip Navigation



Carcinogenesis Advance Access published online on January 3, 2008
Carcinogenesis, doi:10.1093/carcin/bgm283
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
29/3/519    most recent
bgm283v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gatz, S. A.
Right arrow Articles by Wiesmüller, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gatz, S. A.
Right arrow Articles by Wiesmüller, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Susanne A. Gatz1,*, Marlen Keimling2, Cindy Baumann2, Thilo Dörk3, Klaus-Michael Debatin1, Simone Fulda1 and Lisa Wiesmüller2,*

1 University Children's Hospital, Eythstr. 24, D-89075 Ulm, Germany
2 Department of Obstetrics and Gynecology of the University of Ulm, Prittwitzstr. 43, D-89075 Ulm, Germany
3 Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

* Corresponding authors: Susanne A. Gatz, University Children's Hospital, Eythstr. 24, D-89075 Ulm, Germany; E-mail: susanne.gatz{at}uniklinik-ulm.de, phone:0049/731/50057268, Lisa Wiesmüller, 2 Department of Obstetrics and Gynecology of the University of Ulm, Prittwitzstr. 43, D-89075 Ulm, Germany; E-mail: lisa.wiesmueller{at}uni-ulm.de, phone: 0049/731/50058800

Resveratrol (RV) inhibits tumor initiation, promotion and progression which has mainly been explained by its properties in cell cycle control and apoptosis induction. So far, ambiguous observations have been published regarding its influence on genomic stability. To study RV's effects on DNA double-strand break (DSB) repair we applied the established EGFP and I-Sce I based assay system on RV-treated lymphoblastoid cell lines (LCLs). We show that RV inhibits both, homologous recombination (HR) and non homologous end-joining (NHEJ) independently of its known growth and death regulatory functions. Using (i) the isogenic cell lines TK6 and WTK1, which differ in their p53 status, (ii) LCLs from patients with ataxia telangiectasia (AT-cells), (iii) shRNA mediated p53 knockdown, and (iv) chemical inhibition of ATM/ATR by caffeine, we established an ATM-p53-dependent pathway of HR inhibition by RV. Additional use of LCLs from Nijmegen breakage syndrome (NBS) patients furthermore provided evidence for an ATM/ATR-Nbs1-dependent inhibition of microhomology-mediated NHEJ (MM-NHEJ) after RV-treatment. We propose that activation of ATM and /or ATR is a central effect of RV. Repression of error-prone recombination subpathways could at least partially explain the chemopreventive effects of this natural plant constituent in animal cancer models.

Key Words: Resveratrol • DNA double-strand break repair • ATM/ATR • p53 • Nbs1

Received August 8, 2007; revised November 30, 2007; accepted December 3, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.