Effects of local sequence on the formation of interstrand DNA cross-links derived from the reaction of an abasic site with a cytosine residue on the opposing strand

Abstract

DNA Interstrand Cross-Links are of special concern due to the difficulty of repair and cytotoxicity of cells associated with these lesions. Interstrand Cross-Links between abasic sites and native nucleobases has shown promise in recent years. A new type of Interstrand Cross-Link between an abasic site and a cytosine residue has shown capability of forming when placed under specific conditions. A mismatched cytosine residue demonstrated cross-linking capabilities up to 69% in acidic conditions. Mismatches on flanking base pairs also showed increased cross-linking capabilities. Cross-linking is also observed under human physiological conditions, demonstrating this lesion’s capability of forming in vivo. Further work in this line of DNA chemistry may result in increased biological relevance and advances in understanding this type of DNA damage.