Take a break--resveratrol in action on DNA.
The phytochemical resveratrol (RV) has become a focus of intense research owing to its roles in promoting longevity and in cancer prevention. As an anticancer agent, RV has primarily been linked to growth and death regulatory pathways. There is now growing evidence that, under physiological conditions, RV additionally contributes to the maintenance of genome stability. Thus, at the stage of DNA damage formation, RV protects the genome as an antioxidant via inhibition of inflammation, suppression of metabolic carcinogen activation, de novo expression of genes that encode detoxifying proteins and possibly even via radical scavenging properties. However, results demonstrating RV-dependent DNA breakage in the presence of Cu(II) ions and inhibition of DNA polymerases alpha and delta produced some controversy regarding RV's role as a caretaker compound. Significantly, recent studies have revealed that activation of ataxia telangiectasia mutated and ataxia telangiectasia Rad3 related could be a central effect of RV that underlies cell-cycle regulation and the newly described activation of fidelity control mechanisms in DNA double-strand break repair involving Nbs1 and p53. In this review, we discuss the existing data on RV's direct and indirect effects on genome integrity, in the light of future chemopreventive and chemotherapeutic protocols involving RV or related compounds.
Gatz
Susanne A
SA
University Children's Hospital, Eythstrasse 24, D-89075 Ulm, Germany.
Wiesmüller
Lisa
L
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D013267:Stilbenes; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000077185:Resveratrol