License to glue

Replication of DNA and cohesion of the resultant sister chromatids are two activities that must be coordinated. Now, Peter Gillespie and Tatsuya Hirano (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY) have found that the same “licensing” process that gets DNA ready for replication is also necessary to allow loading of the cohesin complex responsible for sister chromatid cohesion.

Gillespie and Hirano used the sequence of yeast cohesin-loading proteins to identify human and frog versions. They confirmed biochemically in frog extracts what had been inferred genetically in yeast: that Scc2 (in frogs via two isoforms) is required for the loading of cohesin onto DNA.

Association of Scc2 with chromatin was inhibited by two treatments that block DNA replication licensing: addition of geminin, a small protein that binds to the prereplication complex protein Cdt1, and depletion of an origin recognition complex subunit. The cyclin-dependent kinase inhibitor p21^CIP1, which inhibits DNA replication initiation, had no such inhibitory effect.

Cohesin may get onto specialized sites such as the centromere and damaged DNA via other mechanisms, but at least in frogs the licensing machinery would make a sensible chaperone to ensure that the glue arrived before duplication. Gillespie and Hirano also suggested that mitotic Cdc2 activity displaced Scc2. Soon afterwards, most of the cohesin is displaced by Polo and Aurora B, two kinases downstream of Cdc2, thus allowing the sister chromatids to be prepared for the onset of anaphase and another cell cycle. ▪

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