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An advance in the understanding of exchanges between DNA molecules during recombination

​Collaborative work between the SBIGeM (I2BC@Saclay) and the Marseille Cancer Research Center, published in Molecular Cell, illuminates the mechanistic basis and genetic control of homologous recombination, a mechanism for repairing DNA breaks responsible for chromosome exchange during meiosis. However, canonical models do not explain the complexity of meiotic recombination profiles and this study, which reconstructs reaction intermediates, constitutes a major advance in the understanding of this mechanism.

Published on 15 May 2018


Meiotic recombination is essential for fertility and allelic shuffling. Canonical recombination models fail to capture the observed complexity of meioticrecombinants. Here, by combining genome-wide meiotic heteroduplex DNApatterns with meiotic DNA double-strand break (DSB) sites, we show that part of this complexity results from frequent template switching during synthesis-dependent strand annealing that yields noncrossovers and from branch migration of double Holliday junction (dHJ)-containing intermediates that mainly yield crossovers. This complexity also results from asymmetric positioning of crossover intermediates relative to the initiating DSB and Msh2-independent conversions promoted by the suspected dHJ resolvase Mlh1-3 as well as Exo1 and Sgs1. Finally, we show that dHJ resolution is biased toward cleavage of the pair of strands containing newly synthesized DNA near the junctions and that this bias can be decoupled from the crossover-biased dHJ resolution. These properties are likely conserved in eukaryotes containing ZMM proteins, which includes mammals.

Read the French version.

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