A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion

Robison, Brett; Guacci, Vincent; Koshland, Douglas

doi:10.1091/mbc.e17-08-0511

Cited by 15 publications

(16 citation statements)

References 51 publications

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“…Failure of the mcd1-V137K mutated cohesin in clustering suggests that Pds5p must be recruited to chromosome-bound cohesin to promote cohesin clustering and cohesion maintenance. In contrast, chromosome-bound cohesin molecules with mcd1p-Q266 or smc3p-D667 bind Pds5p ( Eng et al, 2014 ; Robison et al, 2018 ), which suggests that recruitment of Pds5p to cohesin is not sufficient for cohesin clustering and cohesion maintenance. Taken together, these results are consistent with a mechanism where Pds5p is first recruited to cohesin by Mcd1p linker, and then the Mcd1p ROCC region, together with Smc3p hinge domain, promotes cohesin clustering and cohesion maintenance.…”

Section: Resultsmentioning

confidence: 99%

“…This hypothesis predicts that cohesin mutations that specifically block cohesion maintenance and RDN condensation would likely be defective in cohesin clustering. Only three mutations in yeast cohesin are known to cause defects specifically in cohesion maintenance and RDN condensation ( Eng et al, 2014 ; Robison et al, 2018 ). Two mutations are in the Mcd1p, one in the linker ( mcd1-V137K ) and the other in the regulation of cohesion and condensation (ROCC) domain ( mcd1-Q266 ).…”

Section: Resultsmentioning

confidence: 99%

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Cohesin architecture and clustering in vivo

Xiang

Koshland

2021

eLife

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Cohesin helps mediate sister chromatid cohesion, chromosome condensation, DNA repair and transcription regulation. We exploited proximity-dependent labeling to define the in vivo interactions of cohesin domains with DNA or with other cohesin domains that lie within the same or in different cohesin complexes. Our results suggest both cohesin's head and hinge domains bind to DNA, and cohesin structure is dynamic with differential folding of its coiled coil regions to generate butterfly confirmations. This method also reveals that cohesins form ordered clusters on and off DNA. The levels of cohesin clusters and their distribution on chromosomes are cell cycle-regulated. Cohesin clustering is likely necessary for cohesion maintenance because clustering and maintenance uniquely require the same subset of cohesin domains and the auxiliary cohesin factor Pds5p. These conclusions provide important new mechanistic and biological insights into the architecture of the cohesin complex, cohesin-cohesin interactions, and cohesin's tethering and loop extruding activities.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Cohesin architecture and clustering in vivo

Xiang

Koshland

2021

eLife

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“…Having established that key cohesin regulators function independently of preventing DNA exit through the Smc3p Mcd1p interface, we turned to characterize the function of the interface itself. Mutations in Mcd1p or Smc3p that affect residues in the interface are lethal (Arumugam et al, 2006; Eng et al, 2014; Gligoris et al, 2014; Robison et al, 2018). One such mutation, smc3-L1029R was thought to prevent cohesin binding to DNA because when tagged with GFP, it failed to immunolocalize to the cohesin-rich centromere cluster (Gligoris et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…Chromatin Immunoprecipitation (ChIP) was performed as previously described (Robison et al, 2018). Primers used for ChIP are shown in Supplementary file 2.…”

Section: Methodsmentioning

confidence: 99%

“…Eco1p (Ctf7p) mediated acetylation of the Smc3p K112 K113 head domain residues promotes stable cohesin DNA binding and cohesion (Skibbens et al, 1999; Tóth et al, 1999; Rolef Ben-Shahar et al, 2008; Unal et al, 2008; Bloom et al, 2018). Once cohesion is established, Pds5p promotes cohesion maintenance as well as condensation (Hartman et al, 2000; Stead et al, 2003; Noble et al, 2006; Robison et al, 2018). Wpl1p binds to Pds5p to promote cohesin’s release from DNA and serves to antagonize both cohesion and condensation (Gandhi et al, 2006; Kueng et al, 2006; Rowland et al, 2009; Guacci and Koshland, 2012; Lopez-Serra et al, 2013; Bloom et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Communication between distinct subunit interfaces of the cohesin complex promotes its topological entrapment of DNA

Guacci

Chatterjee

Robison

et al. 2019

eLife

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Cohesin mediates higher order chromosome structure. Its biological activities require topological entrapment of DNA within a lumen(s) formed by cohesin subunits. The reversible dissociation of cohesin’s Smc3p and Mcd1p subunits is postulated to form a regulated gate that allows DNA entry and exit into the lumen. We assessed gate-independent functions of this interface in yeast using a fusion protein that joins Smc3p to Mcd1p. We show that in vivo all the regulators of cohesin promote DNA binding of cohesin by mechanisms independent of opening this gate. Furthermore, we show that this interface has a gate-independent activity essential for cohesin to bind chromosomes. We propose that this interface regulates DNA entrapment by controlling the opening and closing of one or more distal interfaces formed by cohesin subunits, likely by inducing a conformation change in cohesin. Furthermore, cohesin regulators modulate the interface to control both DNA entrapment and cohesin functions after DNA binding.

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The Many Roles of Cohesin in Drosophila Gene Transcription

Dorsett

2019

Trends in Genetics

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The cohesin protein complex mediates sister chromatid cohesion to ensure accurate chromosome segregation, and also influences gene transcription in higher eukaryotes. Modest deficits in cohesin function that do not alter chromosome segregation cause significant birth defects. The mechanisms by which cohesin participates in gene regulation have been studied in Drosophila, revealing that it is involved in gene activation by transcriptional enhancers and epigenetic gene silencing by Polycomb group proteins. Recent studies reveal that early DNA replication origins are important for determining which genes associate with cohesin and suggest that cohesin at replication origins is important for establishing both sister chromatid cohesion and enhancerpromoter communication.

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A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion

Abstract: A screen of cohesin subunit Smc3 reveals that its hinge is a nexus controlling the maintenance of sister chromatid cohesion and condensation.

Cited by 15 publications

References 51 publications

Cohesin architecture and clustering in vivo

Cohesin architecture and clustering in vivo

Communication between distinct subunit interfaces of the cohesin complex promotes its topological entrapment of DNA

The Many Roles of Cohesin in Drosophila Gene Transcription

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