A nuclear pore complex‐associated regulation of SUMOylation in meiosis

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene‐deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin‐like modifier (SUMO)‐specific ubiquitin‐like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1‐related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene‐deleted meiotic cells. The Top2‐12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin‐binding proteins is regulated by the NPC‐bound SUMO‐specific protease and is important for the progression of meiosis. An intact NPC tethers the SUMO‐specific protease Ulp1 at the NPC for keeping nuclear SUMOylation homeostasis. The impaired NPCs release Ulp1 to the cytoplasm, resulting in defective meiosis progression through hyperSUMOylation of the nuclear proteins. Forced localization of Ulp1 at the NPC rescues the defective meiosis.