Cohesin is a Motor that Bends and Compacts DNA

Abstract

Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation and recombination. These long-range interactions depend on cohesin, a ring-shaped ATPase complex first identified for its role in sister chromatid cohesion. Whereas cohesin is thought to mediate cohesion as a passive topological linker, it has been recently shown that cohesin can compact DNA and required for DNA loop formation, but how cohesin can perform these function remains unknown. Using single-molecule imaging and optical force spectroscopy we show that cohesin is a motor that compacts DNA. This function depends on cohesin's ATPase activity and NIPBL, both of which have previously been implicated in loading cohesin onto DNA. We show that NIPBL induces rapid movements between the nucleotide binding domains of cohesin and these movements generate a ∼ 10 nm power stroke against 15 pN force, which is potentially strong enough to bend DNA. Cohesin mutants unable to execute this power stroke are deficient in DNA compaction. We propose that cohesin uses its motor activity to buckle DNA against mechanical rigidity provided by NIPBL. Similar power strokes might be used by other SMC complexes to fold genomic DNA in all kingdoms of life.