Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide- DNA binding in the mouse H-ras gene detected by UvrABC nucleases

James X. Chen, Annie Pao, Yi Zheng, Xiancang Ye, Alexander S. Kisleyou, Rebecca Morris, Thomas J. Slaga, Ronald G. Harvey, Moon Shong Tang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We have found that 7,12-dimethylbenz[a]anthracene-syn-diol epoxide (syn- DMBADE)-modified DNA fragments are sensitive to UvrABC incision. The incisions occur mainly seven bases 5' and four bases 3' of a syn-DMBADE- modified adenine or guanine residue. The kinetics of UvrABC incision at different sequences in a DNA fragment are the same, and the extent of UvrABC incision is proportional to the syn-DMBADE concentration. On the basis of these results, we have concluded that UvrABC incision on syn-DMBADE-DNA adducts is independent of DNA sequence and is quantitative. Using the UvrABC incision method, we have analyzed the syn-DMBADE-DNA binding spectrum in several defined DNA fragments, including the first two exons of the mouse H- ras gene. We have found that both guanine and adenine residues in codons 12, 13, and 61 of the H-ras gene are strong syn-DMBADE binding sites. These results suggest that the initial binding of DMBADE may greatly contribute to the frequency of H-ras mutations. Results from dinucleotide binding analysis indicate that the 5'-nearest neighbor displays a greater effect on syn- DMBADE-DNA binding than the 3'-nearest neighbor.

Original languageEnglish (US)
Pages (from-to)9594-9602
Number of pages9
JournalBiochemistry
Volume35
Issue number29
DOIs
StatePublished - 1996

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    Chen, J. X., Pao, A., Zheng, Y., Ye, X., Kisleyou, A. S., Morris, R., Slaga, T. J., Harvey, R. G., & Tang, M. S. (1996). Sequence preference of 7,12-dimethylbenz[a]anthracene-syn-diol epoxide- DNA binding in the mouse H-ras gene detected by UvrABC nucleases. Biochemistry, 35(29), 9594-9602. https://doi.org/10.1021/bi9604136