A Mechanism for RecA-Promoted Sequence Homology Recognition and Strand Exchange Between Single-Stranded DNA and Duplex DNA, via Triple-Helical Intermediates

Abstract

A central function of RecA protein during homologous recombination is to promote sequence recognition and strand exchange between a stretched and unwound single-stranded DNA, to which it is complexed, and a duplex DNA. By studying the properties of DNA under the conditions of deformation imposed by RecA, we propose a model for recognition and strand exchange at the atomic level, via unusual triple-helical intermediates. In this model, association takes place within a stretched and unwound triple helix of a new type, where the invading single strand occupies the minor groove of the duplex in a parallel orientation. Our calculations indicate that strand exchange within this structure is exothermic and results in a triple helix where the third strand interacts in the major groove, the so-called R-DNA triple helix. Preliminary calculations suggest that sequence homology recognition within the triplex of association is partial and that it is completed during strand exchange and product formation.