The Search for Homology: A Paradigm for Molecular Interactions?

Homologous recombination relies on specific interactions between two homologous DNA molecules. How a DNA sequence finds its homologous target in the complexity of a genome remains a thermo-dynamical challenge. The initial recognition step involves insertion of a single-stranded DNA region into the minor groove of a duplex DNA. It requires a local melting of the double helix for specific base pairing and recognition. A family of recombination proteins, such as the RecA protein of Escherichia coli, stimulates this reaction. The kinetic mechanism of DNA pairing is surprisingly poorly understood. The homologous alignment can occur anywhere along the length of either DNA substrate and is generally completed within a few minutes. We will review different experiments suggesting that the speed and the efficiency of the pairing reaction cannot be simply explained by Brownian movement or molecule sliding, but probably involves more complex mechanisms such as ‘molecular translocations and ‘inchworm local movements.