SMC complexes are guarded by the SUMO protease Ulp2 against SUMO-chain-mediated turnover.

Ivan Psakhye,Dana Branzei

doi:10.1016/j.celrep.2021.109485

Abstract

Structural maintenance of chromosomes (SMCs) complexes, cohesin, condensin, and Smc5/6, are essential for viability and participate in multiple processes, including sister chromatid cohesion, chromosome condensation, and DNA repair. Here we show that SUMO chains targetall three SMC complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover. We uncover that the essential role of the cohesin-associated subunit Pds5 is to counteract SUMO chains jointly with Ulp2. Importantly, fusion of Ulp2 to kleisin Scc1 supports viability of PDS5 null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8. The lethality of PDS5-deleted cells can also be bypassed by simultaneous loss of the proliferating cell nuclear antigen (PCNA) unloader, Elg1, and the cohesin releaser, Wpl1, but only when Ulp2 is functional. Condensin and Smc5/6 complex are similarly guarded by Ulp2 against unscheduled SUMO chain assembly, which we propose to time the availability of SMC complexes on chromatin.

Highlights

Posttranslational modification of proteins with the small ubiquitin-like modifier (SUMO) is essential for eukaryotic cells because it regulates substrate fate by affecting protein interactions, activity, localization, and abundance (Flotho and Melchior, 2013)
We show that SUMO chains target all three structural maintenance of chromosomes (SMC) complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover
Fusion of Ulp2 to kleisin Scc1 supports viability of PDS5 null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8

Summary

Introduction

Posttranslational modification of proteins with the small ubiquitin-like modifier (SUMO) is essential for eukaryotic cells because it regulates substrate fate by affecting protein interactions, activity, localization, and abundance (Flotho and Melchior, 2013). SUMOylation frequently targets entire protein groups, actively engaged in common functions (Jentsch and Psakhye, 2013; Psakhye and Jentsch, 2012), and fosters protein complex formation through SUMO binding to SUMO-interacting motifs (SIMs). SUMO is conjugated to exposed lysines on the substrates leading to monoSUMOylation or, if several lysines are modified, to multiSUMOylation. Mono/ multiSUMOylation may be extended to SUMO chains when lysines of SUMO conjugated to the substrate are being further modified with SUMO, leading to substrate polySUMOylation. SUMO chains may function as a countdown timer if they are assembled on STUbL substrates

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