Understanding the Role of DNA Discontinuities in Promoting Meiotic Crossing Over
Meiosis is a specialized form of cell division that results in the formation of gametes. In most sexually reproducing organisms, meiotic recombination is a crucial step in meiosis during which homologous chromosomes physically interact and exchange genetic information. The final DNA recombination intermediate in this process is the double Holliday Junction (dHJ). A major question in the meiosis field is the mechanism through which dHJs are cleaved in a biased manner to create crossover products. Mlh1-Mlh3, the nuclease responsible for resolving the majority of dHJs in budding yeast, is not intrinsically capable of recognizing and cleaving dHJs in a biased manner. This observation, combined with genetic screens revealing a wide variety of crossover promoting factors, indicates that other proteins may interact at the dHJ to promote biased resolution. Here, I describe work demonstrating genetic evidence in baker’s yeast that the Rad2/XPG family nuclease Exo1 promotes meiotic crossing over by protecting DNA nicks from ligation. I describe findings that structural elements in Exo1 that interact with DNA, such as those required for the bending of DNA during nick/flap recognition, are critical for its role in crossing over. In addition, meiotic overexpression of Cdc9 ligase reduces the crossover levels of exo1 DNA-binding mutants to levels that approach the