Free radical adducts induce alterations in DNA cytosine methylation

Sigmund A. Weitzman*, Patrick W. Turk, Deborah Howard Milkowski, Karen Kozlowski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

Methylation of cytosines in DNA is important for the regulation of expression of many genes. During carcinogenesis, normal patterns of gene methylation can be altered. Oxygen radical injury, shown to damage DNA in a variety of ways associated with cancer development and other conditions, has been suggested to affect DNA methylation, but a mechanism has not been demonstrated. Using oligonucleotides containing the common oxygen radical adduct 8-hydroxyguanine to replace guanine, we found that the enzymatic methylation of adjacent cytosines is profoundly altered. Furthermore, there is a high degree of positional specificity with respect to this effect. Thus, free radical injury may explain some of the altered methylation observed during carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1261-1264
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number4
DOIs
StatePublished - Feb 15 1994

ASJC Scopus subject areas

  • General

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