Meiotic recombination: breaking the genome to save it

Meiotic recombination is initiated in diploid germline cells by the programmed introduction of hundreds of DNA double strand breaks (DSBs) along chromosomes. These DSBs are then repaired by homologous recombination, one of the outcomes being the crossovers, where homologous chromosome arms are exchanged. Meiotic crossing overs are necessary for gamete viability. Errors in meiotic crossover formation are the major source of aneuploidies leading to sterility and chromosomal diseases such as Trisomy 21. Meiotic recombination is also an important source of genetic diversity, generated through the crossovers that shuffle existing combination of alleles, but also through the unidirectional events called conversions that take place at all meiotic recombination sites.

We have recently uncovered a new function of the poorly characterized mismatch repair complex, MutLbeta (Mlh1-Mlh2 in budding yeast), in meiotic recombination. We found that it interacts with recombination proteins to regulate their activity and limit the extent of genetic material exchanged between homologs at each meiosis.

This illustrates the remarkable diversity of DNA processes involving the mismatch repair MutL complexes, and suggests that mechanisms exist to prevent an excess of genetic exchange at meiosis, maybe to preserve favorable genetic combinations.