Similia similibus: pairing of homologous chromosomes driven by the physicochemical properties of DNA.

Abstract

Genetic recombination in eukaryotes requires the pairing of homologous chromosomes to allow precise molecular exchanges between chromosome pairs at intertwined structures called Holliday junctions, the formation of which requires the action of the RecA protein. The mechanism behind the precise pairing of structures as long as chromosomes remains mysterious. In yeast, during the initial phases of meiosis, chromosomes are paired at approximately 65 kilobase intervals via paranemic interactions that do not involve strand breakage nor the intervention of analogs of the RecA protein. It has been proposed that these paranemic interactions could occur between G-rich chromosomal regions, but putting in register stretches of homologous sequences hundreds of kb long remains challenging. Recent developments on the theory of the physicochemical properties of DNA in aqueous solutions, in presence of di- or multivalent counterions, leads to the prediction that molecules with the same sequence tend to pair spontaneously by paranemic interactions depending on the electrostatic properties of DNA. Experimental support for this prediction has now been provided in vitro with naked DNA. This newly discovered property of DNA duplexes may thus provide a clue to solve the puzzle of the premeiotic pairing.