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

Psakhye, Ivan; Branzei, Dana

doi:10.1016/j.celrep.2021.109485

Cited by 16 publications

(24 citation statements)

References 73 publications

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“…SUMO-targeted ubiquitin ligases (STUbLs) are ubiquitin ligases that recognize SUMOmodified proteins. A STUbL consisting of the Slx8 ubiquitin ligase and the associated protein Slx5 functions in proteasome-mediated turnover of several proteins associated with DNA replication, repair, and chromosome structure (57)(58)(59). Our model of the Slx5-Slx8 complex (fig.…”

Section: Complexes Involving Ubiquitin and Small Ubiquitin-like Modif...mentioning

confidence: 99%

Computed structures of core eukaryotic protein complexes

Humphreys

Pei

Baek

et al. 2021

Science

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361

356

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Deep learning for protein interactions The use of deep learning has revolutionized the field of protein modeling. Humphreys et al . combined this approach with proteome-wide, coevolution-guided protein interaction identification to conduct a large-scale screen of protein-protein interactions in yeast (see the Perspective by Pereira and Schwede). The authors generated predicted interactions and accurate structures for complexes spanning key biological processes in Saccharomyces cerevisiae . The complexes include larger protein assemblies such as trimers, tetramers, and pentamers and provide insights into biological function. —VV

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Section: Complexes Involving Ubiquitin and Small Ubiquitin-like Modif...mentioning

confidence: 99%

Computed structures of core eukaryotic protein complexes

Humphreys

Pei

Baek

et al. 2021

Science

Self Cite

361

356

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“…Pds5 is necessary in order to protect the Mcd1 protein from SUMOylation and STUbL-dependent degradation (20, 21, 66). Deletion of both CLN2 and ELG1, or overexpression of MCD1 from a plasmid, contributes to increase Mcd1 levels.…”

Section: Discussionmentioning

confidence: 99%

“…STUbL-dependent degradation (20,21,66). Deletion of both CLN2 and ELG1, or overexpression of MCD1 from a plasmid, contributes to increase Mcd1 levels.…”

Section: Pds5 Is Necessary In Order To Protect the Mcd1 Protein From ...mentioning

confidence: 99%

“…The importance of Pds5 in blocking cohesin poly-SUMOylation was demonstrated by identifying mutations in SUMO and SUMO-modifying enzymes that suppress the inviability of Pds5 deficiency. However, other phenotypes of Pds5 deficiency were not suppressed (20)(21)(22) indicating that regulating the SUMO status of cohesin is only one function of Pds5.…”

Section: Introductionmentioning

confidence: 95%

“…In addition, Pds5 maintains cohesion, at least in part, by antagonizing the polySUMO-dependent degradation of cohesin (20, 21) and thereby stabilizing the complex. Pds5 binding to cohesin also promotes removal of unacetylated cohesin from chromosomes because Pds5 is a scaffold for Wpl1’s interaction with cohesin (12).…”

Section: Introductionmentioning

confidence: 99%

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S. cerevisiae cells can grow without the Pds5 cohesin subunit

Choudhary

Itzkovich

Alonso-Pérez

et al. 2022

Preprint

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During DNA replication, the newly created sister chromatids are held together until their separation at anaphase. The cohesin complex is in charge of creating and maintaining sister-chromatid cohesion (SCC) in all eukaryotes. In S. cerevisiae cells, cohesin is composed of two elongated proteins, Smc1 and Smc3, bridged by the kleisin Mcd1/Scc1. The latter also acts as a scaffold for three additional proteins, Scc3/Irr1, Wpl1/Rad61, and Pds5. Although the HEAT-repeat protein Pds5 is essential for cohesion, its precise function is still debated. Deletion of the ELG1 gene, encoding a PCNA unloader, can partially suppress the temperature-sensitive pds5-1 allele, but not a complete deletion of PDS5. We carried out a genetic screen for high copy number suppressors and another for spontaneously arising mutants, allowing the survival of a pds5Δ elg1Δ strain. Our results show that cells remain viable in the absence of Pds5 provided that there is both an elevation in the level of Mcd1 (which can be due to mutations in the CLN2 gene, encoding a G1 cyclin), and an increase in the level of SUMO-modified PCNA on chromatin (caused by lack of PCNA unloading in elg1Δ mutants). The elevated SUMO-PCNA levels increase the recruitment of the Srs2 helicase, which evicts Rad51 molecules from the moving fork, creating ssDNA regions that serve as sites for increased cohesin loading and SCC establishment. Thus, our results delineate a double role for Pds5 in protecting the cohesin ring and interacting with the DNA replication machinery.IMPORTANCESister chromatid cohesion is vital for faithful chromosome segregation, chromosome folding into loops, and gene expression. A multisubunit protein complex known as cohesin holds the sister chromatids from S-phase until the anaphase stage. In this study, we explore the function of the essential cohesin subunit Pds5 in the regulation of sister chromatid cohesion. We performed two independent genetic screens to bypass the function of the Pds5 protein. We observe that Pds5 protein is a cohesin stabilizer, and elevating the levels of Mcd1 protein along with SUMO-PCNA accumulation on chromatin can compensate for the loss of the PDS5 gene. In addition, Pds5 plays a role in coordinating the DNA replication and sister chromatid cohesion establishment. This work elucidates the function of cohesin subunit Pds5, the G1 cyclin Cln2, and replication factors PCNA, Elg1 and Srs2 in the proper regulation of sister chromatid cohesion.

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