SCFCdc4ubiquitin ligase regulates synaptonemal complex formation during meiosis

AbstractHomologous chromosomes pair with each other during meiosis, culminating in the formation of the synaptonemal complex (SC), which is coupled with meiotic recombination. In this study, we showed that a meiosis-specific depletion mutant of a cullin (Cdc53) of the SCF (Skp-Cullin-F-box) ubiquitin ligase, which plays a critical role in cell cycle regulation during mitosis, is deficient in SC formation, but is proficient in the formation of crossovers, indicating uncoupling of meiotic recombination with SC formation in the mutant. Furthermore, the deletion of thePCH2gene encoding a meiosis-specific AAA+ ATPase suppresses SC-assembly defect induced byCDC53depletion. On the other hand, thepch2 cdc53double mutant is defective in meiotic crossover formation, suggesting the SC assembly with unrepaired DSBs. A temperature-sensitive mutant of theCDC4, which encodes a F-box protein of the SCF, shows similar meiotic defects to theCDC53depletion mutant. These suggest that SCFCdc4, probably SCFCdc4-dependnet protein ubiquitylation, regulates and collaborates with Pch2 in SC assembly and meiotic recombination.SummaryDuring meiosis, homologous chromosomes pair with each other and form the synaptonemal complex (SC). In this study, components of the SCF (Skp-Cullin-F-box) ubiquitin ligase, Cdc53 and Cdc4, are required for SC formation. A meiosis-specific AAA+ ATPase Pch2 antagonize the functions of Cdc53 and Cdc4 for proper SC assembly.