RSC Adv.2016 6(110):108255-108264

Whether the amino-imino tautomerism of 2-aminopurine is involved into its mutagenicity? Results of a thorough QM investigation.

Ol’ha O. Brovarets’ and Horacio Pérez-Sánchezc



The biologically important issue of whether the amino-imino tautomerism of 2-aminopurine (2AP) is the cause of the replication and incorporation point errors induced by this mutagen, has been debated for a long time in the literature. Exploring by quantum-mechanical methods the ability of the irregular pairs formed by the H-bonding of the imino tautomer of the 2-aminopurine (2AP*) with canonical DNA bases to acquire enzymatically-competent conformation that guarantees their successful incorporation into the structure of the DNA double helix by the high-fidelity DNA-polymerase, we came to the conclusion that 2AP tautomerism is not implicated into the origin of the replication point errors induced by this mutagen. We have authentically established that 2AP* mutagenic tautomer is able to induce only one single incorporation mistake, namely transversion, by pairing through the two N1H···O6 and N1H···N2 H-bonds with guanine (G) DNA base into the wobble (w) G·2AP*(w) pair. At this, the formed pair acquires enzymatically-competent Watson-Crick (WC) conformation by following the pathway of the tautomeric and conformational transformations G·2AP*(w)→G*·2AP(w)→ G·2AP(WC)→ G·2APsyn →G·2APsyn(WC). In this case, the long G·2AP(WC) wrong pair, stabilized by the participation of the three C6H···O6, N1H···N1 and N2H···N2 H-bonds, acts as a predecessor of the enzymatically-competent conformation- the G·2APsyn(WC) mispair.