Abstract

Meiosis increases genetic diversity, yet the genome complement needs to be stable to ensure offspring viability. Both small ubiquitin‐like modifier (SUMO) and ubiquitin have been reported to participate in meiotic regulation, yet functions of the SUMO‐ubiquitination crosstalk in meiosis remain unclear. Here, it is reported that a SUMO‐targeted ubiquitin ligase, Slx8p, promotes accurate chromosome segregation during meiosis, since the deletion of SLX8 leads to increased aneuploidy due to a defect in synaptonemal complex (SC) component degradation. Both the RING domain and SUMO interacting motifs of Slx8p are essential for meiotic progression and maintaining spore viability, and the expression of tetraubiquitin fused with SUMO partially rescues meiotic defects in the SLX8‐deletion strain. Furthermore, Slx5p‐Slx8p can directly add ubiquitin to SUMOylated Zip1p and Ecm11p, and forced degradation of Ecm11p partially rescues the sporulation defects of the SLX8 deletion strain. These findings provide a mechanism for SC disassembly and reveal that the crosstalk between SUMOylation and ubiquitination facilitates accurate chromosome segregation by promoting SC component degradation during meiosis.

Highlights

  • To further confirm our finding, we evaluated the meiotic progression in WT, slx5Δ, slx8Δ, and slx5Δ slx8Δ strains, and found that sporulation in slx5Δ, slx8Δ, and slx5Δ slx8Δ strains showed a delay at the early stages of meiosis (Figure 1B)

  • As it was difficult to detect the spore formation in slx5Δ and slx5Δ slx8Δ cells after incubating in sporulation medium for 24 h (Figure S1A, Supporting Information), we examined the spore viability in slx8Δ cells and found most of the tetrad-derived spores in the slx8Δ mutant cells were inviable (Figure 1C,D)

  • As Slx5p-Slx8p is responsible for the turnover of SUMOylated proteins by promoting their ubiquitination,[25,39] and the degradation of Zip1p and Ecm11p was delayed in slx8Δ cells (Figure 3C–F), we speculated that Slx8p might promote the degradation of Zip1p and Ecm11p to promote meiotic progression

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Summary

Slx5p-Slx8p Is the Key STUbL that Regulates Meiosis

Three STUbLs have been reported to play roles in budding yeast, including Uls1p, Rad18p, and Slx5p-Slx8p.[25]. As it was difficult to detect the spore formation in slx5Δ and slx5Δ slx8Δ cells after incubating in sporulation medium for 24 h (Figure S1A, Supporting Information), we examined the spore viability in slx8Δ cells and found most of the tetrad-derived spores in the slx8Δ mutant cells were inviable (Figure 1C,D). This result indicates Slx8p should be required for proper chromosome segregation during meiosis, and we selected Slx8p for further investigation

The Disruption of SLX8 Impairs Meiotic Cell Division
SLX8 Deletion Leads to Extended Prophase I and Metaphase I
Slx8p Is Required for SC Component Degradation
Slx8p Is Required for Accurate Chromosome Segregation during Meiosis
Slx8p’s Role in Meiosis Is Dependent on Its STUbL Activity
Slx8p Facilitates SC Components Degradation via SUMO-Ubiquitination Crosstalk
Slx5p-Slx8p Catalyzes the Ubiquitination of SUMOylated Zip1p and Ecm11p
Ecm11p Is the Key Substrate of Slx8p during Meiosis
Discussion
Experimental Section
Conflict of Interest
Full Text
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