The AP lyase activity of the bifunctional DNA glycosylase endonuclease III generates a 3’-deoxyribose cleavage product (3’dR, a 3’-terminal abasic site). Here, we report that the 3’dR cleavage product can form a novel DNA interstrand crosslink by reaction with the exocyclic <i>N<sup>6</sup></i>-amino group of an adenine residue on the opposing DNA strand (Scheme-1). We have characterized the structure of the cross-link using gel electrophoresis, LC-MS, and hydroxyl-radical foot-printing. We will also describe potential cellular mechanisms for the repair of this novel tandem lesion involving formation of an interstrand crosslink at a strand break in duplex DNA.

Interstrand DNA cross-links generated by an Endo III-derived base excision repair intermediate

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.