Insights into homology search from cryo-EM structures of RecA-DNA recombination intermediates.

The fundamental reaction in homologous recombination is the exchange of strands between two homologous DNA molecules. This reaction is carried out by the RecA family of ATPases that polymerize on ssDNA to form a presynaptic filament. This filament then binds to dsDNA to form a synaptic filament, a key intermediate that mediates the search for homology and subsequent strand exchange to produce a new heteroduplex. A recent cryo-EM analysis of synaptic filaments has now shed light on this process. The dsDNA strands are separated on binding to the filament. One strand is sequestrated while the other is freed to sample pairing with the ssDNA. Homology, through heteroduplex formation, promotes dsDNA opening. Lack of homology suppresses it, keeping local synapses short so that multiple synapses can form and increasing the probability of encountering homology.