Discovery and synthesis of new UV-induced intrastrand C(4-8)G and G(8-4)C photolesions

Martin Münzel; Claudia Szeibert; Andreas F Glas; Daniel Globisch; Thomas Carell

doi:10.1021/ja111304f

Discovery and synthesis of new UV-induced intrastrand C(4-8)G and G(8-4)C photolesions

J Am Chem Soc. 2011 Apr 13;133(14):5186-9. doi: 10.1021/ja111304f. Epub 2011 Mar 22.

Authors

Martin Münzel¹, Claudia Szeibert, Andreas F Glas, Daniel Globisch, Thomas Carell

Affiliation

¹ Center for Integrated Protein Science (CIPS(M)) at the Department of Chemistry, Ludwig-Maximilians-University Munich , Butenandtstrasse 5-13, 81377 Munich, Germany.

PMID: 21425860
DOI: 10.1021/ja111304f

Abstract

UV irradiation of cellular DNA leads to the formation of a number of defined mutagenic DNA lesions. Here we report the discovery of new intrastrand C(4-8)G and G(8-4)C cross-link lesions in which the C(4) amino group of the cytosine base is covalently linked to the C(8) position of an adjacent dG base. The structure of the novel lesions was clarified by HPLC-MS/MS data for UV-irradiated DNA in combination with chemical synthesis and direct comparison of the synthetic material with irradiated DNA. We also report the ability to generate the lesions directly in DNA with the help of a photoactive precursor that was site-specifically incorporated into DNA. This should enable detailed chemical and biochemical investigations of these lesions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytosine / chemistry
DNA / chemistry*
DNA / genetics
Photochemical Processes
Ultraviolet Rays*

Substances

Cytosine
DNA