Ubiquitin-proteasome system regulates pro-crossover protein dynamics during meiosis in Caenorhabditis elegans.

Crossover (CO) formation ensures accurate segregation of homologous chromosomes during the first meiotic division. The pro-crossover proteins are essential for crossover formation and undergo dynamic changes during meiotic prophase I, although the underlying regulatory mechanism is largely unknown. Here, we found that the ubiquitin-proteasome system (UPS) plays a pivotal role in orchestrating pro-crossover protein dynamics and crossover patterning during meiosis in Caenorhabditis elegans. Knockdown of either the ubiquitin-activating enzyme E1 or the proteasome resulted in elevated pro-crossover protein levels and crossover designation. Impairing ubiquitination, but not proteasome activity, led to persistent association of pro-crossover proteins on meiotic chromosomes, a process mediated by the CDC-48UFD-1/NPL-4 segregase. Utilizing a hypomorphic allele of cosa-1, a well-characterized pro-crossover protein-encoding gene, we further demonstrate that the UPS restricts crossover formation. Collectively, our findings reveal a multilayered UPS-mediated regulatory network that maintains proper pro-crossover protein dynamics, thereby coordinating crossover formation with meiotic chromosome segregation.