Structure of a Stable Interstrand DNA Cross-Link Involving a β-N-Glycosyl Linkage Between an N⁶-dA Amino Group and an Abasic Site

Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

“…In contrast, reaction of the directly opposing adenine residue with the AP site would “pinch” the width of the double-helix in a manner that requires significant structural reorganizations (e.g., “zippering” of bases near the ICL) . Finally, the NMR structure shows that formation of the dA-AP ICL is associated with unpairing of the adenine residue from its Watson–Crick partner thymine …”

“…A foundation for understanding the structural aspects of the dC-AP cross-link may be found in a recently solved NMR structure of the dA-AP ICL . This NMR structure illustrates how the helical twist of DNA places the NH 2 group of adenine in close proximity for reaction with the AP aldehyde when the nucleobase is offset one nucleotide to the 3′-side of the AP site on the opposing strand.…”

“…A foundation for understanding the structural aspects of the dC-AP cross-link may be found in a recently solved NMR structure of the dA-AP ICL. 51 This NMR structure illustrates how the helical twist of DNA places the NH 2 group of adenine in close proximity for reaction with the AP aldehyde when the nucleobase is offset one nucleotide to the 3′-side of the AP site on the opposing strand. In contrast, reaction of the directly opposing adenine residue with the AP site would "pinch" the width of the double-helix in a manner that requires significant structural reorganizations (e.g., "zippering" of bases near the ICL).…”

“…52 Finally, the NMR structure shows that formation of the dA-AP ICL is associated with unpairing of the adenine residue from its Watson−Crick partner thymine. 51 With the NMR structure of the dA-AP ICL as a guidepost, it may be useful to pose the question: Why does a cytosine residue that is paired with its Watson−Crick partner guanine fail to generate the dC-AP ICL? First, the unpairing of the C-G base pair required for formation of the dC-AP ICL would be energetically more costly than unpairing the adenine residue from its partner thymine residue base pair as observed for the dA-AP ICL.…”

Hybridization-specific chemical reactions to create interstrand crosslinking and threaded structures of nucleic acids

“…4). [31][32][33][34][35][36] In this reaction, the aldehyde group of the AP site reacts with the exocyclic amino group of the purine base in the opposite strand of the duplex to provide an imine-derived linkage (Fig. 4A).…”