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This study reveals that the ubiquitin-proteasome system (UPS) regulates the dynamics of pro-crossover proteins during meiosis in C. elegans, a process critical for proper chromosome segregation. The researchers found that reducing UPS activity leads to elevated levels of pro-crossover proteins and altered crossover formation patterns, with ubiquitination and the CDC-48 segregase complex controlling how long these proteins remain associated with chromosomes. The findings demonstrate that UPS provides multilayered control over crossover formation, ensuring accurate chromosome distribution during reproductive cell division.
Why it matters
Understanding the molecular mechanisms controlling crossover formation has implications for fertility research and genetic diversity. Defects in meiotic crossover regulation can lead to chromosome segregation errors, which cause infertility, miscarriages, and genetic disorders such as Down syndrome in humans.
by Hongtao Zhang, Wenqing Liang, Meng Li, Yuejun Yang, Lei He, Wencong Nan, Guoteng Liu, Bin Wang, Ye Hong
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.