Cohesin’s DNA Exit Gate Is Distinct from Its Entrance Gate and Is Regulated by Acetylation
Sister chromatid cohesion is mediated by entrapment of sister DNAs by a tripartite ring composed of cohesin’s Smc1, Smc3, and α-kleisin subunits. Cohesion requires acetylation of Smc3 by Eco1, whose role is to counteract an inhibitory (antiestablishment) activity associated with cohesin’s Wapl subun...
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Veröffentlicht in: | Cell 2012-08, Vol.150 (5), p.961-974 |
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Sprache: | eng |
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Zusammenfassung: | Sister chromatid cohesion is mediated by entrapment of sister DNAs by a tripartite ring composed of cohesin’s Smc1, Smc3, and α-kleisin subunits. Cohesion requires acetylation of Smc3 by Eco1, whose role is to counteract an inhibitory (antiestablishment) activity associated with cohesin’s Wapl subunit. We show that mutations abrogating antiestablishment activity also reduce turnover of cohesin on pericentric chromatin. Our results reveal a “releasing” activity inherent to cohesin complexes transiently associated with Wapl that catalyzes their dissociation from chromosomes. Fusion of Smc3’s nucleotide binding domain to α-kleisin’s N-terminal domain also reduces cohesin turnover within pericentric chromatin and permits establishment of Wapl-resistant cohesion in the absence of Eco1. We suggest that releasing activity opens the Smc3/α-kleisin interface, creating a DNA exit gate distinct from its proposed entry gate at the Smc1/3 interface. According to this notion, the function of Smc3 acetylation is to block its dissociation from α-kleisin. The functional implications of regulated ring opening are discussed.
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► Yeast cohesin releases DNA through a releasing activity associated with its subunits ► DNA escapes from cohesin via the opening Smc3/kleisin interface ► Eco1-mediated Smc3 acetylation blocks releasing activity ► Cohesin ring has separate gates for DNA entry and exit
Cohesin rings entrap and then release sister chromatids using conformational changes in distinct ring subunits to create the entrance and exit sites. |
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ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/j.cell.2012.07.028 |