Mapping of UV photoproducts along the c-jun promoter in UV-irradiated human cells
Journal Article
·
· Environmental and Molecular Mutagenesis
OSTI ID:88921
- Beckman Research Institute of the City of Hope, Duarte, CA (United States)
The formation of UV photoproducts is implicated in the induction of mutations and the development of skin cancer. Cyclobutane dimers and (6-4) photoproducts are the two major causes of mutagenic DNA photoproducts produced by UV irradiation. It is known that the distribution of these DNA adducts is not only influenced by DNA sequence but also by chromatin structure. To analyse possible effects of chromatin structure on the photoproduct spectrum, we have compared the distribution of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidine photoproducts, along the c-jun promoter in UV-irradiated HeLa cells, with that obtained from irradiated purified DNA. After UV irradiation, cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidine photoproducts were converted into DNA strand breaks by treatment with hot pyrimidine or T4 endonuclease v/photolyase cleavage. Ligation-mediated PCR was then used to map both types of UV photoproducts at the DNA sequence level. Photoproduct frequency within transcription factor binding sties was suppressed or enhanced relative to naked DNA. Photofootprints were localized to an AP1 like sequence (nt. -71 to -64), a CCAAT box element (nt. -91 to -87), and SP1 sequence (nt. -123 to -118), a nuclear factor jun (NF-jun) site (nt. -140 to -132) and a second AP1 like sequence (nt. -190 to -183). These findings have possible implications on molecular mechanisms of mutagenesis in the human genome.
- OSTI ID:
- 88921
- Report Number(s):
- CONF-9405324--; CNN: Grant ES06070
- Journal Information:
- Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.23 Vol. 23; ISSN 0893-6692; ISSN EMMUEG
- Country of Publication:
- United States
- Language:
- English
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