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Cohesin releases DNA through asymmetric ATPase-driven ring opening

ABSTRACT: Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin’s Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover an unexpected functional asymmetry within the heart of cohesin’s highly conserved ABC-like ATPase machinery and show that an activity associated with one of cohesin’s two ATPase sites drives DNA release from cohesin rings. This key mechanism is conserved from yeast to humans. We propose that Eco1 locks cohesin rings around the sister chromatids by counteracting an asymmetric cohesin-associated ATPase activity.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE76891 | GEO | 2016/02/18

SECONDARY ACCESSION(S): PRJNA308861

REPOSITORIES: GEO

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Cohesin releases DNA through asymmetric ATPase-driven ring opening

Project description:Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesinâs Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover an unexpected functional asymmetry within the heart of cohesinâs highly conserved ABC-like ATPase machinery and show that an activity associated with one of cohesinâs two ATPase sites drives DNA release from cohesin rings. This key mechanism is conserved from yeast to humans. We propose that Eco1 locks cohesin rings around the sister chromatids by counteracting an asymmetric cohesin-associated ATPase activity. Effect of mutations in Smc1 and Smc3 on cohesin loading onto chromosomes

2016-02-18 | E-GEOD-76891 | biostudies-arrayexpress

Sister chromatid cohesion establishment by acetylation

Project description:Cohesion between sister chromatids depends on the chromosomal cohesin complex and allows the spindle apparatus in mitosis to recognize replicated chromosomes for segregation into daughter cells. Sister chromatid cohesion is established concomitant with DNA replication, and requires the essential Eco1 protein, a replication fork-associated acetyl transferase. The mechanism by which Eco1 establishes sister chromatid cohesion is not known. Here, we show that the cohesin subunit Smc3 is acetylated in an Eco1-dependent manner during S phase to establish sister chromatid cohesion. We isolated spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast, and identified the suppressor mutations from the hybridization pattern of genomic DNA on oligonucleotide tiling arrays. An acetylation mimicking mutation of a conserved lysine in Smc3 to asparagine (K113N) makes Eco1 dispensable for cell growth, indicating that Smc3 acetylation is Eco1’s only essential function. We identified a second set of eco1-1 suppressor mutations in the budding yeast ortholog of the cohesin regulator Wapl (Wpl1/Rad61). Wapl destabilizes cohesin on chromosomes, and Eco1-dependent Smc3 acetylation during S-phase might render cohesin resistant to Wapl. Our results clarify the role of Eco1 in the establishment of sister chromatid cohesion, and suggest that Eco1 modifies cohesin to stabilize an Eco1-independent cohesion establishment reaction.

2008-07-24 | GSE11527 | GEO

Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1

Project description:Cohesin’s association with chromosomes is determined by loading dependent on the Scc2/4 complex and release due to Wapl. We show here that Scc2 also actively maintains cohesin on chromosomes during G1. It does so by blocking a Wapl-independent release reaction that requires opening the cohesin ring at its Smc3/Scc1 interface as well as the D loop of Smc1’s ATPase. The Wapl-independent release mechanism is switched off as cells activate Cdk1 and enter G2/M and cannot be turned back on without cohesin’s dissociation from chromosomes. The latter phenomenon enabled us to show that in the absence of release mechanisms, cohesin rings that have already captured DNA in a Scc2-dependent manner before replication no longer require Scc2 to capture sister DNAs during S phase.

2019-06-06 | GSE132221 | GEO

Budding yeast Wapl controls sister chromatid cohesion maintenance and the chromosome condensation status [expression]

Project description:Cohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation. The Affymetrix Yeast Genome 2.0 Arrays were used to analyze the expression profile of wt and waplM-bM-^HM-^F cells.

2012-11-22 | E-GEOD-42458 | biostudies-arrayexpress

The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism

Project description:Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the 3D genome. ESCO1 restricts the length of chromatin loops and architectural stripes, while HDAC8 promotes the extension of such loops and stripes. This role in controlling loop length turns out to be distinct from the canonical role of cohesin acetylation that protects against WAPL-mediated DNA release. We reveal that acetylation rather controls cohesin’s interaction with PDS5A to restrict chromatin loop length. Our data supports a model in which this PDS5A-bound state acts as a brake that enables the pausing and restart of loop enlargement. The cohesin acetylation cycle hereby provides punctuation in the process of genome folding.

2022-03-14 | PXD032185 | Pride

Releasing activity disengages cohesin’s Smc3/Scc1 interface in a process blocked by acetylation

Project description:Sister chromatid cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin’s Scc1, Smc1, and Smc3 subunits is generated during S and eventually destroyed at anaphase through cleavage of Scc1 by separase. Throughout the cell cycle, cohesin’s association with chromosomes is controlled by opposing activities: loading by the Scc2/4 complex and release by a separase independent releasing activity. Co-entrapment of sister DNAs during replication is accompanied by acetylation of Smc3 by Eco1, which blocks releasing activity and ensures that sisters remain stably connected. Because fusion of Smc3 to Scc1 prevents release and bypasses the requirement for Eco1, we suggested that release is mediated by disengagement of the Smc3/Scc1 interface. We now show that all mutations capable of bypassing Eco1, be they in cohesin’s Smc1, Smc3, Scc1,Wapl, Pds5, or Scc3 subunits, greatly reduce dissociation of N-terminal cleavage fragments of Scc1 (NScc1) from Smc3. We show that this process involves interaction between Smc ATPase heads and is inhibited by Smc3 acetylation

2016-02-18 | GSE76890 | GEO

Budding yeast Wapl controls sister chromatid cohesion maintenance and the chromosome condensation status [BrdU-ChIP].

Project description:Cohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation. The Affymetrix Saccharomyces cerevisiae Chip Tiling 1.0F Arrays were used to analyze the incorporation of BrdU in Saccharomyces cerevisiae in S-phase arrested cells.

2012-11-22 | E-GEOD-42456 | biostudies-arrayexpress

Budding yeast Wapl controls sister chromatid cohesion maintenance and the chromosome condensation status [PK-ChIP]

Project description:Cohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation. The Affymetrix Saccharomyces cerevisiae Chip Tiling 1.0R Arrays were used to analyze the binding pattern of Scc1 along the genome of Saccharomyces cerevisiae in late G1 and metaphase arrested cells.

2012-11-22 | E-GEOD-42457 | biostudies-arrayexpress

Budding yeast Wapl controls sister chromatid cohesion maintenance and the chromosome condensation status [expression]

2012-11-22 | GSE42458 | GEO

Budding yeast Wapl controls sister chromatid cohesion maintenance and the chromosome condensation status [PK-ChIP]

2012-11-22 | GSE42457 | GEO