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The cohesin ring uses its hinge to organize DNA using non-topological as well as topological mechanisms

ABSTRACT: As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is a perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads onto chromosomes but fails to form cohesion, loading is accompanied by entrapment of individual DNAs. However, cohesin with a hinge whose positively charged lumen has been neutralized not only loads onto and translocates along chromatin but also organizes it into chromatid-like threads, despite largely failing to entrap DNAs inside its ring. Thus, cohesin engages chromatin in both a non-topological and a topological manner. Further, mutation of three highly conserved lysines within the Smc1 hinge abolishes all loading without affecting cohesin’s initial recruitment to centromers or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin’s hinge driven by cycles of ATP hydrolysis.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE105005 | GEO | 2018/04/23

REPOSITORIES: GEO

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Transport of DNA within cohesin involves clamping on top of engaged heads by Scc2 and entrapment within the ring by Scc3

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2020-09-03 | GSE156616 | GEO

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [Hi-C]

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Releasing activity disengages cohesinâs Smc3/Scc1 interface in a process blocked by acetylation

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2016-02-18 | E-GEOD-76890 | biostudies-arrayexpress

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Isw1 contributes to cohesin association with centromeres and pericentromeric regions

Project description:Cohesin is a highly conserved, multiprotein complex whose canonical function is to hold sister chromatids together to ensure accurate chromosome segregation. Cohesin association with chromatin relies on the separate Scc2-Scc4 complex that enables cohesin ring opening and topological entrapment of sister DNAs. Cohesin loading at centromeres also requires the CTF19 kinetochore subcomplex that recruits Scc2-Scc4, ensuring efficient and targeted cohesin binding. After loading at centromeres, cohesin rapidly translocates to neighboring pericentromeric regions. In an attempt to better understand how sister chromatid cohesion is regulated, we performed a proteomic screen in budding yeast that identified the Isw1 chromatin remodeler as a cohesin binding partner. We found that while cohesin can associate with both Isw1-containing complexes, ISW1a and ISW1b, however only ISW1a localizes to centromeres. There, ISW1a utilizes its chromatin remodeling activity to allow efficient translocation of cohesin loaded through CTF19 at centromeres to pericentromeres. Consistently, lack of Isw1 results in cohesin and cohesin loader retainment at CENs and periCENs. Interestingly, lack of Isw1 resulted in changes in the nucleosomal landscape at the CENs and pericentromeric regions, suggesting that chromatin organization may be a crucial determinant of cohesin loading. Finally, we provide evidence that the role of ISW1a at the CENs is to restrict the activity of the RSC complex. Taken together, our results support the notion of a key role of chromatin environment for cohesin functions.

2023-05-16 | GSE232315 | GEO

Crosslinking/mass spectrometry (CLMS) analysis of Cohesin complex

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2020-08-04 | PXD018608 | Pride

Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5

Project description:In addition to sharing with condensin an ability to organize DNA into chromatids, cohesin regulates enhancer-promoter interactions and confers sister chromatid cohesion. Association with chromosomes is regulated by hook-shaped HEAT repeat proteins that Associate With its Kleisin (Scc1) subunit (HAWKs), namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently displaces Pds5 during loading. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity, loading, and translocation while Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states, one with Pds5 bound to Scc1 that is not able to hydrolyse ATP efficiently but is capable of release from chromosomes and another in which Scc2, transiently replacing Pds5, stimulates the ATP hydrolysis necessary for loading and translocation away from loading sites.

2018-07-17 | GSE106182 | GEO

Folding of cohesin's coiled coil is important for Scc2/4-induced association with chromosomes

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