SCF^Cdc4ubiquitin ligase regulates synaptonemal complex formation during meiosis

Abstract

Homologous 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) in the SCF (Skp-Cullin-F-box) ubiquitin ligase, which plays a critical role in cell cycle regulation during mitosis, is deficient in SC formation. However, the mutant is proficient in forming crossovers, indicating the uncoupling of meiotic recombination with SC formation in the mutant. Furthermore, the deletion of the PCH2 gene encoding a meiosis-specific AAA+ ATPase suppresses SC-assembly defects induced by CDC53 depletion. On the other hand, the pch2 cdc53 double mutant is defective in meiotic crossover formation, suggesting the assembly of SC with unrepaired DNA double-strand breaks. A temperature-sensitive mutant of CDC4, which encodes an F-box protein of SCF, shows meiotic defects similar to those of the CDC53-depletion mutant. These results suggest that SCFCdc4, probably SCFCdc4-dependent protein ubiquitylation, regulates and collaborates with Pch2 in SC assembly and meiotic recombination.

The organization, regulation, and biological functions of the synaptonemal complex

“… 44 Depletion of cell division control protein 53 (Cdc53), a cullin in the Skp-Cullin-F-box (SCF) ubiquitin ligase family, results in SC polycomplex formation. 45 Moreover, SUMOylated SC components extracellular mutant protein 11 (Ecm11) and Zip1 can be recognized by heterodimeric Slx8p-Slx5p SUMO-targeted ubiquitin ligase (STUbL) complex and degraded. 46 …”

“… 65 In budding yeast, SC assembly defects caused by SCF component Cdc53 depletion can be suppressed in pch2/cdc53 double mutants. 45 In the Brassica rapa plant, pch2 mutants achieve only partial synapsis. 66 Similarly, Trip13 mutation that severely impairs TRIP13 function causes synapsis defects in mice.…”

FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis

“…In budding yeast, a F-box protein Cdc4 acts as a substrate subunit of SCF durimg meiotic prophase. SCF Cdc4 is assumed to regulate SC assembly by counteracting the Pch2 (TRIP13 in mammals)-dependent negative action that induces SC disassembly (Zhu et al, 2021). It is proposed that SCF Cdc4 targets the putative negative regulator of SC assembly toward degradation, and in turn stabilizes SC.…”

“…In Drosophila female, SkpA, a SKP1 homolog, is required for the assembly and/or the maintenance of SC (Barbosa et al, 2021). In budding yeast Saccharomyces cerevisiae, depletion of Cdc53 that encodes Cullin resulted in defects in SC formation (Zhu et al, 2021). Thus, SCF is involved in the process of homolog synapsis during meiotic prophase in diverse organisms.…”

“…In rice plant Oryza sativa, mutants of MEIOTIC F-box MOF (He et al, 2016) and another Fbox ZYGO1 (Zhang et al, 2017) showed defects in DNA double-strand break (DSB) repair and bouquet formation during meiotic prophase. In budding yeast, temperature sensitive mutant of Cdc4 that encodes F-box protein showed defective SC formation and DSB repair (Zhu et al, 2021). In Drosophila female, depletion of Slmb (βTrcp) and CG6758 (Fbxo42) caused impaired assembly and/or premature disassembly of SC (Barbosa et al, 2021).…”