On the mechanism of RecA-mediated repair of double-strand breaks: no role for four-strand DNA pairing intermediates.

RecA protein will bind to a gapped duplex DNA molecule and promote a DNA strand exchange with a second homologous linear duplex. A double-strand break in the second duplex is efficiently bypassed in the course of these reactions. We demonstrate that the bypass of double-strand breaks is not explained by a mechanism involving homologous interactions between two duplex DNA molecules, but instead requires the ATP-mediated generation of DNA torsional stress brought about by the action of RecA. The results suggest new pathways for the repair of double-strand breaks and underline the need for new paradigms to explain the alignment of homologous DNAs during genetic recombination.