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The cohesin ring concatenates sister DNA molecules

Abstract

Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin. Cohesin’s Scc1, Smc1 and Smc3 subunits form a tripartite ring structure, and it has been proposed that cohesin holds sister DNA molecules together by trapping them inside its ring. To test this, we used site-specific crosslinking to create chemical connections at the three interfaces between the three constituent polypeptides of the ring, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produced dimeric DNA–cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNA molecules.

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Figure 1: Making covalently closed cohesin rings.
Figure 2: Covalent cohesin circularization creates SDS-resistant minichromosome DNA dimers.
Figure 3: Covalent circularization of cohesin holds individual DNAs together.
Figure 4: Minichromosomes are cohesed by single cohesin rings.

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Acknowledgements

We thank S. Gruber for help with the design of cysteine mutations, and P. Fowler, D. Ivanov, V. Katis and all members of the Nasmyth laboratory for advice and discussions. This work was supported by the Medical Research Council, the Wellcome Trust and Cancer Research UK.

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Correspondence to Kim Nasmyth.

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Haering, C., Farcas, AM., Arumugam, P. et al. The cohesin ring concatenates sister DNA molecules. Nature 454, 297–301 (2008). https://doi.org/10.1038/nature07098

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