Research Article

Characterization of a DNA exit gate in the human cohesin ring

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Science  21 Nov 2014:
Vol. 346, Issue 6212, pp. 968-972
DOI: 10.1126/science.1256904

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Abstract

Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin’s proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin’s ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.

A cohesin ring around two DNA strands

Holding together homologous sister chromosome pairs is a vital requirement during cell division and DNA repair. A special complex, called cohesin, forms a ring made of three different proteins and functions to hold together the two sister DNA strands. Gligoris et al. and Huis in 't Veld et al. identified a specific protein-protein interface within the cohesin ring that forms a DNA exit gate. Mutations in this interface prevented cohesion between sister chromatids. Thus, the cohesin ring must indeed encircle the two DNA strands to hold them together.

Science, this issue p. 963, p. 968

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