PCNA promotes context-specific sister chromatid cohesion establishment separate from that of chromatin condensation

Zuilkoski, Caitlin M.; Skibbens, Robert V.

doi:10.1080/15384101.2020.1804221

Cited by 8 publications

(12 citation statements)

References 87 publications

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“…Note that several studies now point to the importance of both Eco1 and cohesin dimerization/clustering during the establishment of sister chromatid cohesion and DNA loop formation, although other studies suggest that at least cohesins may act in monomeric form (Cattoglio et al, 2019; Shi et al, 2020; Kulemzina et al, 2012, Tong and Skibbens, 2014; Eng et al, 2015; Zhang et al, 2008; Xiang and Koshland, 2021; Skibbens et al, 1999; Kim et al, 2019; Liu et al, 2020; Shi et al, 2020). As a final class of suppressors, ELG1 deletion and PCNA overexpression, both of which result in elevated levels of chromatin-bound PCNA, suppress eco1 mutant cell phenotypes through increased Eco1 recruitment to the DNA replication fork (Skibbens et al, 1999; Moldovan et al, 2006; Maradeo and Skibbens, 2010; Parnas et al, 2010; Song et al, 2012; Bender et al, 2020; Zuilkoski and Skibbens, 2020a). Cln2 appears distinct from each of these suppressor pathways and thus creates a new category of cohesin regulators.…”

Section: Discussionmentioning

confidence: 99%

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

Buskirk

Skibbens

2022

Preprint

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Eco1/Ctf7 is a highly conserved acetyltransferase that activates cohesin complexes and is critical for sister chromatid cohesion, chromosome condensation, DNA damage repair, nucleolar integrity, and gene transcription. Mutations in the human homolog of ECO1 (ESCO2/EFO2), or in genes that encode cohesin subunits, result in severe developmental abnormalities and intellectual disabilities referred to as Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS), respectively. In yeast, deletion of ECO1 results in cell inviability. Co-deletion of RAD61 (WAPL in humans), however, produces viable yeast cells. These eco1 rad61 double mutants, however, exhibit a severe temperature-sensitive growth defect, suggesting that Eco1 or cohesins respond to hyperthermic stress through a mechanism that occurs independent of Rad61. Here, we report that deletion of the G1 cyclin CLN2 rescues the temperature sensitive lethality otherwise exhibited by eco1 rad61 mutant cells, such that the triple mutant cells exhibit robust growth over a broad range of temperatures. While Cln1, Cln2 and Cln3 are functionally redundant G1 cyclins, neither CLN1 nor CLN3 deletions rescue the temperature-sensitive growth defects otherwise exhibited by eco1 rad61 double mutants. We further provide evidence that CLN2 deletion rescues hyperthermic growth defects independent of START and impacts the state of chromosome condensation. These findings reveal novel roles for Cln2 that are unique among the G1 cyclin family and appear critical for cohesin regulation during hyperthermic stress.

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Section: Discussionmentioning

confidence: 99%

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

Buskirk

Skibbens

2022

Preprint

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“…PCNA overexpression in temperature-sensitive Eco1 mutants partially rescues viability and cohesion defects [ 59 , 158 ]. In line with this, the growth defects of a PCNA-binding mutant (Eco1 PIP ) can be rescued by fusing Eco1 PIP to Fen1 and (to a lesser extent) to Cdc9, which both function on the lagging strand in a late stage of DNA replication [ 89 ].…”

Section: Establishment Of Sister Chromatid Cohesionmentioning

confidence: 99%

The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks

Schie

Lange

2021

Cells

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The cohesin complex facilitates faithful chromosome segregation by pairing the sister chromatids after DNA replication until mitosis. In addition, cohesin contributes to proficient and error-free DNA replication. Replisome progression and establishment of sister chromatid cohesion are intimately intertwined processes. Here, we review how the key factors in DNA replication and cohesion establishment cooperate in unperturbed conditions and during DNA replication stress. We discuss the detailed molecular mechanisms of cohesin recruitment and the entrapment of replicated sister chromatids at the replisome, the subsequent stabilization of sister chromatid cohesion via SMC3 acetylation, as well as the role and regulation of cohesin in the response to DNA replication stress.

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“…It is possible that loading at condensates sets a starting point to accumulate cohesin and recruit other factors that are required for cohesion maintenance (Figure 7). An interesting candidate for such a factor is the cohesin acetylase Eco1, which was previously shown to be recruitable by DNA-protein-cocondensates in other contexts (Zuilkoski & Skibbens, 2020). It is possbile that Scc2/4 is exchanged by these factors within the condensates once its task is fulfilled as it is known that Scc2/4 is not required for cohesion maintenance (Srinivasan et al, 2019).…”

Section: Ideas and Speculationmentioning

confidence: 99%

The loader complex Scc2/4 forms co-condensates with DNA as loading sites for cohesin

Zernia

Kamp

Stigler

2021

Preprint

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The genome is organized by diverse packaging mechanisms like nucleosome formation, loop extrusion and phase separation, which all compact DNA in a dynamic manner. Phase separation additionally drives protein recruitment to condensed DNA sites and thus regulates gene transcription. The cohesin complex is a key player in chromosomal organization that extrudes loops to connect distant regions of the genome and ensures sister chromatid cohesion after S-phase. For stable loading onto the DNA and for activation, cohesin requires the loading complex Scc2/4. As the precise loading mechanism remains unclear, we investigated whether phase separation might be the initializer of the cohesin recruitment process. We found that, in absence of cohesin, budding yeast Scc2/4 forms phase separated co-condensates with DNA, which comprise liquid-like properties shown by droplet shape, fusion ability and reversibility. We reveal in DNA curtain and optical tweezer experiments that these condensates are built by DNA bridging and bending through Scc2/4. Importantly, Scc2/4-mediated condensates recruit cohesin efficiently and increase the stability of the cohesin complex. We conclude that phase separation properties of Scc2/4 enhance cohesin loading by molecular crowding, which might then provide a starting point for the recruitment of additional factors and proteins.

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PCNA promotes context-specific sister chromatid cohesion establishment separate from that of chromatin condensation

Cited by 8 publications

References 87 publications

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae

The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks

The loader complex Scc2/4 forms co-condensates with DNA as loading sites for cohesin

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