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. 2013 Dec 2;52(49):12879-82.
doi: 10.1002/anie.201307580. Epub 2013 Oct 15.

Detection and characterization of 1,2-dibromoethane-derived DNA crosslinks formed with O(6) -alkylguanine-DNA alkyltransferase

Goutam Chowdhury  1 , Sung-Hee Cho, Anthony E Pegg, F Peter Guengerich
Affiliations

Detection and characterization of 1,2-dibromoethane-derived DNA crosslinks formed with O(6) -alkylguanine-DNA alkyltransferase

Goutam Chowdhury et al. Angew Chem Int Ed Engl. .

Abstract

A combination of chemical modifications and LC-tandem MS was used for the structure elucidation of various ethylene crosslinks of DNA with O(6) -alkylguanine-DNA alkyltransferase (AGT, see picture). The elucidation of the chemical structures of such DNA-protein crosslinks is necessary to understand mechanisms of mutagenesis.

Keywords: DNA adducts; DNA damage; DNA-protein crosslinks; hydrogenation; mutations.

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Figures

Figure 1
Figure 1
Yields of the various types of DPCs formed in the presence of AGT and 14C-DBE. a) Total DPCs (labile + non-labile). b) Labile DPCs. c) Non-labile DPCs. d) Relative yields of labile DPCs, N7-G adducts measured as N7-Et guanine. e) Yields of various non-labile DPCs (N1-dG, N2-dG, and O6-dG and N6-dA) measured as their corresponding Et adducts (n = 3, ± SD).
Scheme 1
Scheme 1
Mechanism of DBE derived crosslink formation by AGT
Scheme 2
Scheme 2
Flow chart for the detection and quantitation of various DPC and DNA adducts
See this image and copyright information in PMC

References

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