Meiotic Holliday junctions are cleaved to yield either crossovers or non-crossovers (gene conversions). The resolvase or resolvases responsible for cleavage are unknown but a resolvase complex in human cells may include SLX4 and/or GEN1.
Two classes of crossovers have been defined: class I crossovers are dependent on the MutL homologs, Mlh1 and Mlh3 as well as residual Msh4 and Msh5 (Baker et al. 1996, Anderson et al. 1999, Santucci-Darmanin et al. 2000, Lipkin et al. 2002, Moens et al. 2002, Marcon and Moens 2003, Kolas et al. 2005, de Boer et al. 2006, Moens et al. 2007, Svetlanov et al. 2008) while class II crossovers are dependent on the MUS81-EME1 endonuclease (Holloway et al. 2008).
Class I crossovers constitute 90-95% of all crossovers, and correspond to meiotic nodules that contain Mlh1and Mlh3. These arise as a subset of the many hundreds of Msh4/Msh5-positive meiotic nodules that arise at the time of double Holliday junction formation. What happens to all the other meiotic nodules is not clear, but they most likely follow a second pathway that results in non-crossovers (or gene conversions). Mlh1 and Mlh3 form heterodimers that bind mismatches in duplex DNA. In mouse Mlh1 is required for crossovers but not for non-crossover resolution of Holliday junctions. About 10% of early recombination nodules are somehow selected to become class I crossover events by losing Blm (and probably associated Top3a) and gaining Mlh1 and Mlh3.
The selection of sites for class II crossovers follows an, as yet, unknown pathway, but almost certainly stems from the same initiating D-loop intermediate.
In the process known as crossover interference, the presence of a crossover nodule inhibits formation of nearby crossover nodules so that crossovers are not clustered and each chromosome bivalent has at least one crossover. Crossover interference is seen among nodules at two stages: Rpa-containing nodules during late zygonema and Mlh1-containing nodules during pachynema (de Boer et al. 2006). Class II crossovers are not subject to interference constraints.
The checkpoint kinase Cdk2 colocalizes with Mlh1 and is required for synapsis and recombination, however its function is unknown (Ashley et al. 2001, Viera et al. 2009).