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Replication of N2,3-Ethenoguanine by DNA Polymerases

Authors


  • This work was supported in part by United States Public Health Service grants R01 ES010546, R01 ES010375, P01 ES05355, T32 ES007028, and P30 ES000267. We acknowledge beamline scientists Drs. Zdzislaw Wawrzak and David Smith (LS-CAT, Argonne National Laboratory) for helping collecting crystallographic data and Albena Kozekova for assistance in oligonucleotide purification.

Abstract

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Damaged goods: The unstable DNA adduct N2,3-ethenoguanine, a product of both exposure to the carcinogen vinyl chloride and of oxidative stress, was built into an oligonucleotide, using an isostere strategy to stabilize the glycosidic bond. This modification was then used to examine the cause of mutations by DNA polymerases, in terms of both the biochemistry of the lesion and a structure of the lesion within a polymerase (see scheme).

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