A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices

A number of studies have concluded that strand exchange between a RecA-comp lexed DNA single strand and a homologous DNA duplex occurs via a single-str and invasion of the minor groove of the duplex. Using molecular modeling, w e have previously demonstrated the possibility of forming a parallel triple helix in which the single strand interacts with the intact duplex in the m inor groove, via novel base interactions (Bertucat et al., J. Biomol. Struc t Dynam. 16:535-546). This tripler is stabilized by the stretching and unwi nding imposed by RecA. In the present study, we show that the bases within this tripler are appropriately placed to undergo strand exchange. Strand ex change is found to be exothermic and to result in a triple helix in which t he new single strand occupies the major groove. This structure, which can b e equated to so-called R-form DNA, can be further stabilized by compression and rewinding. We are consequently able to propose a detailed, atomic-scal e model of RecA-promoted strand exchange. This model, which is supported by a variety of experimental data, suggests that the role of RecA is principa lly to prepare the single strand for its future interactions, to guide a mi nor groove attack on duplex DNA, and to stabilize the resulting, stretched tripler, which intrinsically favors strand exchange. We also discuss how th is mechanism can incorporate homologous recognition.