Exo1 recruits Cdc5 polo kinase to MutL? to ensure efficient meiotic crossover formation.

Crossovers generated during the repair of programmed meiotic double-strand breaks must be tightly regulated to promote accurate homolog segregation without deleterious outcomes, such as aneuploidy. The Mlh1-Mlh3 (MutL?) endonuclease complex is critical for crossover resolution, which involves mechanistically unclear interplay between MutL? and Exo1 and polo kinase Cdc5. Using budding ...
yeast to gain temporal and genetic traction on crossover regulation, we find that MutL? constitutively interacts with Exo1. Upon commitment to crossover repair, MutL?-Exo1 associate with recombination intermediates, followed by direct Cdc5 recruitment that triggers MutL? crossover activity. We propose that Exo1 serves as a central coordinator in this molecular interplay, providing a defined order of interaction that prevents deleterious, premature activation of crossovers. MutL? associates at a lower frequency near centromeres, indicating that spatial regulation across chromosomal regions reduces risky crossover events. Our data elucidate the temporal and spatial control surrounding a constitutive, potentially harmful, nuclease. We also reveal a critical, noncatalytic role for Exo1, through noncanonical interaction with polo kinase. These mechanisms regulating meiotic crossovers may be conserved across species.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Binding Sites, Cell Cycle Proteins, Chromosomes, Fungal, Crossing Over, Genetic, Exodeoxyribonucleases, Fungal Proteins, Meiosis, Models, Biological, Models, Molecular, MutL Proteins, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Recombination, Genetic
Proc Natl Acad Sci U S A
Date: Dec. 01, 2019
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