DOI: 10.1073/pnas.95.15.8508. 3, N 4 -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase

3, N 4 -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase

10.1073/pnas.95.15.8508

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Exocyclic DNA adducts are generated in cellular DNA by various industrial pollutants such as the carcinogen vinyl chloride and by endogenous products of lipid peroxidation. The etheno derivatives of purine and pyrimidine bases 3, N 4 -ethenocytosine (ɛC), 1, N 6 -ethenoadenine (ɛA), N 2 ,3-ethenoguanine, and 1, N 2 -ethenoguanine cause mutations. The ɛA residues are excised by the human and the Escherichia coli 3-methyladenine-DNA glycosylases (ANPG and AlkA proteins, respectively), but the enzymes repairing ɛC residues have not yet been described. We have identified two homologous proteins present in human cells and E. coli that remove ɛC residues by a DNA glycosylase activity. The human enzyme is an activity of the mismatch-specific thymine-DNA glycosylase (hTDG). The bacterial enzyme is the double-stranded uracil-DNA glycosylase (dsUDG) that is the homologue of the hTDG. In addition to uracil and ɛC-DNA glycosylase activity, the dsUDG protein repairs thymine in a G/T mismatch. The fact that ɛC is recognized and efficiently excised by the E. coli dsUDG and hTDG proteins in vitro suggests that these enzymes may be responsible for the repair of this mutagenic lesion in vivo and be important contributors to genetic stability.

Bibliography

Saparbaev, M., & Laval, J. (1998). 3, N 4 -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase. Proceedings of the National Academy of Sciences, 95(15), 8508â8513.

Authors 2

Murat Saparbaev (first)
Jacques Laval (additional)

References 46 Referenced 138

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:41 p.m.)
Indexed	2 days, 1 hour ago (Aug. 29, 2025, 5:48 a.m.)
Issued	27 years, 1 month ago (July 21, 1998)
Published	27 years, 1 month ago (July 21, 1998)
Published Online	27 years, 1 month ago (July 21, 1998)
Published Print	27 years, 1 month ago (July 21, 1998)

Funders 0

None

BibTeX

@article{Saparbaev_1998, title={3, N 4 -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.15.8508}, DOI={10.1073/pnas.95.15.8508}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Saparbaev, Murat and Laval, Jacques}, year={1998}, month=jul, pages={8508–8513} }

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