期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 8, 页码 4266-4280出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab214
关键词
-
资金
- National Cancer Institute of the National Institutes of Health [R01CA40463]
- Department of Chemistry atWashington University
CPDs are major DNA products caused by UV light absorption, leading to C to T mutations associated with skin cancers. A new pathway to CPDs in melanocytes has been discovered, involving a chemisensitized pathway that increases mutagenesis by affecting the percentage of C-containing CPDs. Triplet sensitization in CPD formation favors TT over C-containing sites, with significant differences between norfloxacin and acetone due to their triplet energies.
Cyclobutane pyrimidine dimers (CPDs) are the major products of DNA produced by direct absorption of UV light, and result in C to T mutations linked to human skin cancers. Most recently a new pathway to CPDs in melanocytes has been discovered that has been proposed to arise from a chemisensitized pathway involving a triplet sensitizer that increases mutagenesis by increasing the percentage of C-containing CPDs. To investigate how triplet sensitization may differ from direct UV irradiation, CPD formation was quantified in a 129-mer DNA designed to contain all 64 possible NYYN sequences. CPD formation with UVB light varied about 2-fold between dipyrimidines and 12-fold with flanking sequence and was most frequent at YYYR and least frequent for GYYN sites in accord with a charge transfer quenching mechanism. In contrast, photosensitized CPD formation greatly favored TT over C-containing sites, more so for norfloxacin (NFX) than acetone, in accord with their differing triplet energies. While the sequence dependence for photosensitized TT CPD formation was similar to UVB light, there were significant differences, especially between NFX and acetone that could be largely explained by the ability of NFX to intercalate into DNA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据