Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 May 4;8(3):261-267.
doi: 10.1080/19491034.2017.1295200. Epub 2017 Feb 27.

The torments of the cohesin ring

Alap P Chavda  1 , Keven Ang  1 , Dmitri Ivanov  1   2   3   4
Affiliations
Review

The torments of the cohesin ring

Alap P Chavda et al. Nucleus. .

Abstract

Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a "collapsed" rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The "collapsed" conformation plays a role in cohesin ring assembly and its loading on the DNA. Here we speculate about the mechanism of cohesin's conformational transitions in relation to its loading on the DNA and draw parallels with other Smc-like complexes.

Keywords: ATPase; acetyltransferase; chromosomes; cohesin; sister chromatid cohesion.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Collapsed conformation of cohesin ring is involved in cohesin complex assembly and its loading on the DNA. (A) Schematic illustrating a hypothetical mechanism of cohesin loading on the DNA. Smc1 and Smc3 arms are likely to be acetylated during or after protein synthesis. The post-translationally modified arms intertwine, bringing the head domains together and facilitating their tethering via Scc1. ATP hydrolysis by the heads leads to their separation from each other while still being connected by Scc1. Head separation results in the unraveling of the coiled coils, which might be facilitated by the binding of the cohesin loader Scc2 and the opening of the cohesin ring at the hinge. The opened hinge binds to DNA, which leads to DNA being imported into the ring. After the cohesin ring embraces the DNA, the Smc arms can still interact with each other, restricting the ring opening and inhibiting its ability to slide along the DNA. The interaction between the arms might be regulated by chromatin-associated acetylases/deacetylases. (B) The Smc arms can be cross-linked on DNA. Strains expressing a photo-crosslinkable version of Smc3 with K318 (mid-coiled coil) or E209 (head-proximal) substituted for p-benzoylphenylalanine (BPA) were UV-irradiated, cell lysates were fractionated into the supernatant and chromatin-containing pellet and Smc1-Myc was detected by western blot. Cdc28 and Hmo1 were detected as the markers of the soluble and chromatin-associated fractions, respectively.
See this image and copyright information in PMC

Erratum for

  • Extra View to: I Kulemzina, K Ang, X Zhao, J-T Teh, V Verma, S Suranthran, A P Chavda, R G Huber, B Eisenhaber, F Eisenhaber, J Yan, D Ivanov.. A reversible association between Smc coiled coils is regulated by lysine acetylation and is required for cohesin association with the DNA. Mol Cell 2016; 63:1044-1054; https://doi.org/10.1016/j.molcel.2016.08.008 doi: 10.1016/j.molcel.2016.08.008

References

    1. Marston AL. Chromosome segregation in budding yeast: sister chromatid cohesion and related mechanisms. Genetics 2014; 196:31-63; PMID:24395824; https://doi.org/ 10.1534/genetics.112.145144 - DOI - PMC - PubMed
    1. Dorsett D, Strom L. The ancient and evolving roles of cohesin in gene expression and DNA repair. Curr Biol: CB 2012; 22:R240-50; PMID:22497943; https://doi.org/ 10.1016/j.cub.2012.02.046 - DOI - PMC - PubMed
    1. Merkenschlager M, Nora EP. CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation. Annu Rev Genomics Hum Genet 2016; 17:17-43; PMID:27089971; https://doi.org/ 10.1146/annurev-genom-083115-022339 - DOI - PubMed
    1. Ivanov D, Nasmyth K. A topological interaction between cohesin rings and a circular minichromosome. Cell 2005; 122:849-60; PMID:16179255; https://doi.org/ 10.1016/j.cell.2005.07.018 - DOI - PubMed
    1. Haering CH, Farcas AM, Arumugam P, Metson J, Nasmyth K. The cohesin ring concatenates sister DNA molecules. Nature 2008; 454:297-301; PMID:18596691; https://doi.org/ 10.1038/nature07098 - DOI - PubMed

Publication types

LinkOut - more resources