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Interstrand DNA–DNA Cross-Link Formation Between Adenine Residues and Abasic Sites in Duplex DNA

Price, Nathan E., Johnson, Kevin M., Wang, Jin, Fekry, Mostafa I., Wang, Yinsheng, Gates, Kent S.
Journal of the American Chemical Society 2014 v.136 no.9 pp. 3483-3490
DNA, adenine, aldehydes, crosslinking
The loss of a coding nucleobase from the structure of DNA is a common event that generates an abasic (Ap) site (1). Ap sites exist as an equilibrating mixture of a cyclic hemiacetal and a ring-opened aldehyde. Aldehydes are electrophilic functional groups that can form covalent adducts with nucleophilic sites in DNA. Thus, Ap sites present a potentially reactive aldehyde as part of the internal structure of DNA. Here we report evidence that the aldehyde group of Ap sites in duplex DNA can form a covalent adduct with the N⁶-amino group of adenine residues on the opposing strand. The resulting interstrand DNA–DNA cross-link occurs at 5′-ApT/5′-AA sequences in remarkably high yields (15–70%) under physiologically relevant conditions. This naturally occurring DNA-templated reaction has the potential to generate cross-links in the genetic material of living cells.