Methylglyoxal, an endogenous aldehyde, crosslinks DNA polymerase and the substrate DNA
AUTOR(ES)
Murata-Kamiya, Naoko
FONTE
Oxford University Press
RESUMO
Methylglyoxal, a known endogenous and environmental mutagen, is a reactive α-ketoaldehyde that can modify both DNA and proteins. To investigate the possibility that methylglyoxal induces a crosslink between DNA and DNA polymerase, we treated a ‘primed template’ DNA and the exonuclease-deficient Klenow fragment (KFexo–) of DNA polymerase I with methylglyoxal in vitro. When the reaction mixtures were analyzed by SDS–PAGE, we found that methylglyoxal induced a DNA–KFexo– crosslink. The specific binding complex of KFexo– and ‘primed template’ DNA was necessary for formation of the DNA–KFexo– crosslink. Methylglyoxal reacted with guanine residues in the single-stranded portion of the template DNA. When 2′-deoxyguanosine was incubated with Nα-acetyllysine or N-acetylcysteine in the presence of methylglyoxal, a crosslinked product was formed. No other amino acid derivatives tested could generate a crosslinked product. These results suggest that methylglyoxal crosslinks a guanine residue of the substrate DNA and lysine and cysteine residues near the binding site of the DNA polymerase during DNA synthesis and that DNA replication is severely inhibited by the methylglyoxal-induced DNA–DNA polymerase crosslink.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55850Documentos Relacionados
- Photocontrol of Alcohol, Aldehyde, and Anthocyanin Production in Apple Skin. 1
- Activity of the Yap1 Transcription Factor in Saccharomyces cerevisiae Is Modulated by Methylglyoxal, a Metabolite Derived from Glycolysis
- Preliminary study of the influence of CO2 extraction conditions on the ester, aldehyde, ketone and hydrocarbon content of grape bagasses from jam production
- RNA-dependent DNA polymerase of an endogenous type C virus of mice: purification and partial characterization.
- Structure of Hepatitis B Dane Particle DNA and Nature of the Endogenous DNA Polymerase Reaction