A chromosome-coupled ubiquitin-proteasome pathway is required for meiotic surveillance

Abstract

Defects in meiotic prophase can cause meiotic chromosome missegregation and aneuploid gamete formation. Meiotic checkpoints are activated in germ cells with meiotic defects, and cells with unfixed errors are eliminated by apoptosis. How such a surveillance process is regulated remains elusive. Here, we report that a chromosome-coupled ubiquitin-proteasome pathway (UPP) regulates meiotic checkpoint activation and promotes germ cell apoptosis in C. elegans meiosis-defective mutants. We identified an F-box protein, FBXL-2, that functions as a core component within the pathway. This chromosome-coupled UPP regulates meiotic DSB repair kinetics and chromosome dynamic behaviors in synapsis defective mutants. Disrupted UPP impairs the axial recruitment of the HORMA domain protein HIM-3, which is required for efficient germ cell apoptosis in synapsis defective mutants. Our data suggest that an efficient chromosome-coupled UPP functions as a part of the meiotic surveillance system by enhancing the integrity of the meiotic chromosome axis.