S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit

Choudhary, Karan; Itzkovich, Ziv; Alonso-Pérez, Elisa; Bishara, Hend; Dunn, Barbara K.; Sherlock, Gavin; Kupiec, Martin

doi:10.1128/mbio.01420-22

Cited by 6 publications

(14 citation statements)

References 69 publications

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“…In a remarkable convergence of studies, however, deletion of CLN2 was found to promote the viability of both eco1Δ rad61Δ at 37°C and pds5Δ elg1Δ cells (83,84). The latter study provided evidence that CLN2 deletion increased Mcd1 levels, such that simply elevating Mcd1 protein levels was sufficient to render viable pds5Δ elg1Δ double mutant cells (83).…”

Section: Resultsmentioning

confidence: 96%

“…Defects in cohesin regulation are also tightly correlated with several forms of cancer (80–82). Despite the importance of cohesin functions, little is known regarding the regulation of cohesins early during the cell cycle, but recent findings confirm that MCD1 expression may be a critical component (83,84). In this study, we identify FDO1 as a novel regulator of MCD1 expression.…”

Section: Introductionmentioning

confidence: 99%

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Fdo1, Fkh1, Fkh2 and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae

Singh,

Skibbens

2024

Preprint

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Cohesins promote proper chromosome segregation, gene transcription, genomic architecture, DNA condensation, and DNA damage repair. Mutations in either cohesin subunit or regulatory genes can give rise to severe developmental abnormalities (such as Robert Syndrome and Cornelia de Lange Syndrome) and also are highly correlated with cancer. Despite this, little is known about cohesin regulation. Eco1 (ESCO2/EFO2 in humans) and Rad61 (WAPL in humans) represent two such regulators but perform opposing roles. Eco1 acetylation of cohesin during S phase, for instance, stabilizes cohesin-DNA binding to promote sister chromatid cohesion. On the other hand, Rad61 promotes the dissociation of cohesin from DNA. While Eco1 is essential,ECO1andRAD61co-deletion results in yeast cell viability, but only within a limited temperature range. Here, we report thateco1 rad61cell lethality is due to reduced levels of the cohesin subunit Mcd1. Results from a suppressor screen further reveals thatFDO1deletion rescues the temperature sensitive (ts) growth defects exhibited byeco1 rad61double mutant cells by increasing Mcd1 levels. Regulation ofMCD1expression, however, appears more complex. Elevated expression ofMBP1, which encodes a subunit of the MBF transcription complex, also rescueseco1 rad61cell growth defects. Elevated expression ofSWI6, however, which encodes the Mbp1-binding partner of MBF, exacerbateseco1 rad61cell growth and also abrogates the Mpb1-dependent rescue. Finally, we identify two additional transcription factors, Fkh1 and Fkh2, that impactMCD1expression. In combination, these findings provide new insights into the nuanced and multi-faceted transcriptional pathways that impactMCD1expression.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Fdo1, Fkh1, Fkh2 and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae

Singh,

Skibbens

2024

Preprint

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“…The anti-recombinase Srs2 helicase recruited by SUMOylated PCNA was recently suggested to work at replication forks to support the viability of elg1 Δ pds5 Δ cells with increased levels of Scc1 (ref. 25 ). We indeed observed that elg1 Δ wpl1 Δ pds5 Δ cells rely on Srs2 for viability when Rad51 recombinase is expressed.…”

Section: Resultsmentioning

confidence: 99%

PCNA recruits cohesin loader Scc2 to ensure sister chromatid cohesion

Psakhye,

Kawasumi,

Abe

et al. 2023

Nat Struct Mol Biol

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Sister chromatid cohesion, established during replication by the ring-shaped multiprotein complex cohesin, is essential for faithful chromosome segregation. Replisome-associated proteins are required to generate cohesion by two independent pathways. One mediates conversion of cohesins bound to unreplicated DNA ahead of replication forks into cohesive entities behind them, while the second promotes cohesin de novo loading onto newly replicated DNA. The latter process depends on the cohesin loader Scc2 (NIPBL in vertebrates) and the alternative PCNA loader CTF18-RFC. However, the mechanism of de novo cohesin loading during replication is unknown. Here we show that PCNA physically recruits the yeast cohesin loader Scc2 via its C-terminal PCNA-interacting protein motif. Binding to PCNA is crucial, as the scc2-pip mutant deficient in Scc2–PCNA interaction is defective in cohesion when combined with replisome mutants of the cohesin conversion pathway. Importantly, the role of NIPBL recruitment to PCNA for cohesion generation is conserved in vertebrate cells.

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“…Pds5 is essential for cell viability, and in its absence, cohesion is lost. A new yeast study showed that cells can live without Pds5 under one of two conditions - overexpression of Mcd1 or an accumulation of the loading clamp PCNA on chromosomes ( Choudhary et al, 2022 ). These modifications stabilize cohesin on chromatin.…”

Section: Open Questions and Concluding Remarksmentioning

confidence: 99%

It’s all in the numbers: Cohesin stoichiometry

Matityahu

Onn²

2022

Front. Mol. Biosci.

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Cohesin, a structural maintenance of chromosome (SMC) complex, organizes chromatin into three-dimensional structures by threading chromatin into loops and stabilizing long-range chromatin interactions. Four subunits in a 1:1:1:1 ratio compose the cohesin core, which is regulated by auxiliary factors that interact with or modify the core subunits. An ongoing debate about cohesin’s mechanism of action regards its stoichiometry. Namely, is cohesin activity mediated by a single complex or cooperation between several complexes that organize into dimers or oligomers? Several investigations that used various experimental approaches have tried to resolve this dispute. Some have convincingly demonstrated that the cohesin monomer is the active unit. However, others have revealed the formation of cohesin dimers and higher-order clusters on and off chromosomes. Elucidating the biological function of cohesin clusters and determining what regulates their formation are just two of the many new questions raised by these findings. We briefly review the history of the argument about cohesin stoichiometry and the central evidence for cohesin activity as a monomer vs. an oligomer. Finally, we discuss the possible biological significance of cohesin oligomerization and present open questions that remain to be answered.

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S. cerevisiae Cells Can Grow without the Pds5 Cohesin Subunit

Abstract: Sister 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.

Cited by 6 publications

References 69 publications

Fdo1, Fkh1, Fkh2 and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae

Fdo1, Fkh1, Fkh2 and the Swi6-Mbp1 MBF complex regulate Mcd1 levels to impact eco1 rad61 cell growth in Saccharomyces cerevisiae

PCNA recruits cohesin loader Scc2 to ensure sister chromatid cohesion

It’s all in the numbers: Cohesin stoichiometry

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