Open AccessFree radical adducts induce alterations in DNAcytosine methylation.
Author(s) -
Sigmund A. Weitzman,
Patrick W. Turk,
Deborah Howard Milkowski,
K.A. Kozlowski
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.4.1261
Subject(s) - methylation , dna methylation , carcinogenesis , guanine , dna , oligonucleotide , gene , biology , chemistry , adduct , microbiology and biotechnology , gene expression , biochemistry , nucleotide , organic chemistry
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.