Impact of carcinogen-DNA adducts on DNA methylation

Elizaveta S. Gromova, Oksana M. Subach, Vladimir B. Baskunov, Nicholas E. Geacintov

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The methylation of DNA at CpG dinucleotides by DNA methyltransferases (MTases) is an epigenetic alteration of the genome that plays an important role in the regulation of gene expression in eukaryotes. Abnormalities in the levels of methylation are one of the hallmarks of tumorigenesis. Polycyclic aromatic hydrocarbons such as benzo[a]pyrene are ubiquitous environmental pollutants that are metabolized in vivo to highly genotoxic and tumorigenic diol epoxides (B[a]PDE). The latter reacts with cellular DNA to form covalent adducts that can, if not removed by cellular DNA repair mechanisms, cause mutations and the initiation of tumorigenesis in animal model systems, and probably in humans. The potential impact of such lesions on DNA methylation has received relatively little attention. Utilizing an in vitro biochemical approach, it is shown that BPDE-derived DNA lesions can alter DNA methylation by prokaryotic MTases M.SssI and M.HhaI and mammalian MTase Dnmt3a at CpG and GCGC sites. These effects depend on the conformational properties of the lesions and their positions within the DNA recognition sequence. The results of these studies suggest that B[a]PDE may initiate cancer not only by genotoxic mechanisms, but might also contribute to tumor development by epigenetic effects that involve changes in DNA methylation status.

Original languageEnglish (US)
Title of host publicationStructural Biology of DNA Damage and Repair
PublisherAmerican Chemical Society
Pages103-116
Number of pages14
ISBN (Print)9780841225749
DOIs
StatePublished - Jun 1 2010

Publication series

NameACS Symposium Series
Volume1041
ISSN (Print)0097-6156
ISSN (Electronic)1947-5918

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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  • Cite this

    Gromova, E. S., Subach, O. M., Baskunov, V. B., & Geacintov, N. E. (2010). Impact of carcinogen-DNA adducts on DNA methylation. In Structural Biology of DNA Damage and Repair (pp. 103-116). (ACS Symposium Series; Vol. 1041). American Chemical Society. https://doi.org/10.1021/bk-2010-1041.ch007