Homologous Pairing between Long DNA Double Helices

TL;DR

This paper proposes a quantum chemistry-based model where homologous double-stranded DNA recognizes each other through quadruplex formation in the major groove, explaining biological recognition mechanisms.

Contribution

It introduces a novel recognition mechanism involving quadruplexes formed by hydrogen bonding in the major groove, supported by computational and experimental data.

Findings

Recognition via quadruplex formation is feasible and consistent with experimental data.

Sequence effects influence the recognition mechanism.

Topoisomerase II may be involved in the homologous pairing process.

Abstract

Molecular recognition between two double stranded (ds) DNA with homologous sequences may not seem compatible with the B-DNA structure because the sequence information is hidden when it is used for joining the two strands. Nevertheless, it has to be invoked to account for various biological data. Using quantum chemistry, molecular mechanics, and hints from recent genetics experiments I show here that direct recognition between homologous dsDNA is possible through formation of short quadruplexes due to direct complementary hydrogen bonding of major groove surfaces in parallel alignment. The constraints imposed by the predicted structures of the recognition units determine the mechanism of complexation between long dsDNA. This mechanism and concomitant predictions agree with available experimental data and shed light upon the sequence effects and the possible involvement of topoisomerase II in the recognition.