The mecanisms of cohesin dynamic interaction with DNA[edit]

The cohesin complex with indicated subunits

Cohesin is a member of the SMC (Structural Maintenance of chromosome) protein family. It is composed of two rode-shaped ATPasic subunits, Smc3 and Smc1, and another subunit, Scc1, belonging to the kleisin protein family. Smc3 and Smc1 interact, with each other on one extremity of their rode-like structure. At the other extremity, the N and C-terminal regions of Scc1 interact with Smc3 and Smc1, respectively, giving to the complex the form of a tri-partite ring.

Cohesin loading and unloading[edit]

Cohesin is known to interact dynamically with DNA via a cycle of entrapment and un-entrapment of chromatin inside the cohesin ring. This dynamic interaction with DNA is regulated by many factors, namely Scc2 and Wpl1. Scc2 is essential for the loading of cohesin onto chromatin, while Wpl1 unloads cohesin from DNA^[1].

During DNA replication, Smc3 acetylation by Eco1 acetyl transferase suppresses the dynamic interaction of cohesin with DNA by preventing Wpl1-mediated cohesin un-loading, allowing then the establishment of duplicated chromatid cohesion. Considering its ring-shapeed structure, unloading from DNA requires the opening of at least one of cohesin interfaces, therefore creating a DNA exit gate. In an attempt to identify DNA exit gate, Nasmyth’ lab showed that Smc3-Scc1 translational fusion prevents Wpl1-dependent cohesion un-loading. This laboratory then concluded that the Wpl1-induced DNA exit gate is the interface between Smc3 and Scc1^[2]. However, one may envisage that the use of fusion protein can introduce biological artifact, therefore the possibility of DNA exiting through either one of cohesin three interfaces (Smc3-Scc1, Smc1-Scc1 or Smc3-Smc1) cannot completely be ruled out.

Formation of DNA loop by cohesin complex[edit]

Cohesin also promotes the formation of chromatin loops by a mechanism that is poorly known^[3]^[4]. However, a model called “loop extrusion” (LE) proposes that cohesin starts by capturing a small DNA that is progressively enlarge by the translocation of cohesin along DNA until reaching a barrier. Previous studies have validated this model and showed that loop enlargement is stimulated by Scc2 and inhibited by Wpl1^[5]^[6]. Considering Wpl1 unloading activity it is possible that Wpl1 inhibits loop enlargement by the opening of either one of cohesin interfaces, then causing the ring to unload from DNA.

References[edit]

^ Ciosk, R.; Shirayama, M.; Shevchenko, A.; Tanaka, T.; Toth, A.; Shevchenko, A.; Nasmyth, K. (2000-02). "Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins". Molecular Cell. 5 (2): 243–254. doi:10.1016/s1097-2765(00)80420-7. ISSN 1097-2765. PMID 10882066. {{cite journal}}: Check date values in: |date= (help)
^ Gruber, Stephan; Arumugam, Prakash; Katou, Yuki; Kuglitsch, Daria; Helmhart, Wolfgang; Shirahige, Katsuhiko; Nasmyth, Kim (2006-11-03). "Evidence that loading of cohesin onto chromosomes involves opening of its SMC hinge". Cell. 127 (3): 523–537. doi:10.1016/j.cell.2006.08.048. ISSN 0092-8674. PMID 17081975.
^ Rao, Suhas S. P.; Huang, Su-Chen; Glenn St Hilaire, Brian; Engreitz, Jesse M.; Perez, Elizabeth M.; Kieffer-Kwon, Kyong-Rim; Sanborn, Adrian L.; Johnstone, Sarah E.; Bascom, Gavin D.; Bochkov, Ivan D.; Huang, Xingfan; Shamim, Muhammad S.; Shin, Jaeweon; Turner, Douglass; Ye, Ziyi (2017-10-05). "Cohesin Loss Eliminates All Loop Domains". Cell. 171 (2): 305–320.e24. doi:10.1016/j.cell.2017.09.026. ISSN 1097-4172. PMC 5846482. PMID 28985562.
^ Dauban, Lise; Montagne, Rémi; Thierry, Agnès; Lazar-Stefanita, Luciana; Bastié, Nathalie; Gadal, Olivier; Cournac, Axel; Koszul, Romain; Beckouët, Frédéric (2020-03-19). "Regulation of Cohesin-Mediated Chromosome Folding by Eco1 and Other Partners". Molecular Cell. 77 (6): 1279–1293.e4. doi:10.1016/j.molcel.2020.01.019. ISSN 1097-4164. PMID 32032532.
^ Davidson, Iain F.; Bauer, Benedikt; Goetz, Daniela; Tang, Wen; Wutz, Gordana; Peters, Jan-Michael (2019-12-13). "DNA loop extrusion by human cohesin". Science (New York, N.Y.). 366 (6471): 1338–1345. doi:10.1126/science.aaz3418. ISSN 1095-9203. PMID 31753851.
^ Bastié, Nathalie; Chapard, Christophe; Dauban, Lise; Gadal, Olivier; Beckouët, Frédéric; Koszul, Romain (2022-06). "Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin-dependent chromatin loops". Nature Structural & Molecular Biology. 29 (6): 575–585. doi:10.1038/s41594-022-00780-0. ISSN 1545-9985. PMID 35710835. {{cite journal}}: Check date values in: |date= (help)

[1] Ciosk, R.; Shirayama, M.; Shevchenko, A.; Tanaka, T.; Toth, A.; Shevchenko, A.; Nasmyth, K. (2000-02). "Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins". Molecular Cell. 5 (2): 243–254. doi:10.1016/s1097-2765(00)80420-7. ISSN 1097-2765. PMID 10882066. {{cite journal}}: Check date values in: |date= (help)

[2] Gruber, Stephan; Arumugam, Prakash; Katou, Yuki; Kuglitsch, Daria; Helmhart, Wolfgang; Shirahige, Katsuhiko; Nasmyth, Kim (2006-11-03). "Evidence that loading of cohesin onto chromosomes involves opening of its SMC hinge". Cell. 127 (3): 523–537. doi:10.1016/j.cell.2006.08.048. ISSN 0092-8674. PMID 17081975.

[3] Rao, Suhas S. P.; Huang, Su-Chen; Glenn St Hilaire, Brian; Engreitz, Jesse M.; Perez, Elizabeth M.; Kieffer-Kwon, Kyong-Rim; Sanborn, Adrian L.; Johnstone, Sarah E.; Bascom, Gavin D.; Bochkov, Ivan D.; Huang, Xingfan; Shamim, Muhammad S.; Shin, Jaeweon; Turner, Douglass; Ye, Ziyi (2017-10-05). "Cohesin Loss Eliminates All Loop Domains". Cell. 171 (2): 305–320.e24. doi:10.1016/j.cell.2017.09.026. ISSN 1097-4172. PMC 5846482. PMID 28985562.

[4] Dauban, Lise; Montagne, Rémi; Thierry, Agnès; Lazar-Stefanita, Luciana; Bastié, Nathalie; Gadal, Olivier; Cournac, Axel; Koszul, Romain; Beckouët, Frédéric (2020-03-19). "Regulation of Cohesin-Mediated Chromosome Folding by Eco1 and Other Partners". Molecular Cell. 77 (6): 1279–1293.e4. doi:10.1016/j.molcel.2020.01.019. ISSN 1097-4164. PMID 32032532.

[5] Davidson, Iain F.; Bauer, Benedikt; Goetz, Daniela; Tang, Wen; Wutz, Gordana; Peters, Jan-Michael (2019-12-13). "DNA loop extrusion by human cohesin". Science (New York, N.Y.). 366 (6471): 1338–1345. doi:10.1126/science.aaz3418. ISSN 1095-9203. PMID 31753851.

[6] Bastié, Nathalie; Chapard, Christophe; Dauban, Lise; Gadal, Olivier; Beckouët, Frédéric; Koszul, Romain (2022-06). "Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin-dependent chromatin loops". Nature Structural & Molecular Biology. 29 (6): 575–585. doi:10.1038/s41594-022-00780-0. ISSN 1545-9985. PMID 35710835. {{cite journal}}: Check date values in: |date= (help)

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