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Many DNA processes require chromosomes to be held together by a ring-shaped complex called cohesin, but despite the importance of this protein, its interaction with DNA has not been reproduced in vitro; here, using purified yeast proteins, cohesin loading is successfully recapitulated, offering mechanistic insight into how the loader complex mediates topological cohesin binding.

Frank Uhlmann discusses how biophysics and electron microscopy studies have shed light on what lies inside chromosomes.

Frank Uhlmann and colleagues show that the yeast Scc2–Scc4 cohesin loader complex is recruited to nucleosome-free regions in the promoters of highly expressed genes by the RSC chromatin remodeling complex and acts to maintain the nucleosome-free status of its binding sites. These findings suggest that human disorders caused by disruption of cohesin or RSC complex function, such as Cornelia de Lange and Coffin-Siris syndromes, could arise from related changes in the nucleosome landscape.

Uhlmann et al. show that the preclinical phase of Alzheimer’s disease may in fact be a relatively late manifestation of a much earlier pathogenic and targetable process of seed formation and propagation.

Frank Uhlmann and colleagues use chromosome conformation capture (Hi-C) to study mitotic chromosome condensation in the fission yeast Schizosaccharomyces pombe, reporting that small chromatin domains in interphase are replaced by fewer and larger domains in mitosis. They show that condensin sets up longer-range DNA interactions that compact and individualize chromosomes while also restraining local chromatin contacts.

The poor correlation between brain Aβ deposition and clinical symptoms in Alzheimer´s disease remains puzzling. Here, the authors show a temporal dissociation of Aβ deposition and neurodegeneration.

A PxL motif is identified in substrates of yeast phosphatase Cdc14. PxL functions as a docking motif for substrates and contributes to the timing of dephosphorylation during mitotic exit.

Chromatin remodelers direct the cohesin loader to nucleosome depleted regions where cohesin accesses chromosomes. Muñoz et al. now show that the cohesin loader in turn is a biochemical activator of a chromatin remodeler, helping to clear nucleosomes

Here, using single molecule experiments, the authors show that the mechanical stability of cohesin encircling DNA is determined by its hinge domain that disengages at ~20 pN force, providing a framework for how cohesin counteracts spindle-generated tension during mitosis.

Separases are crucial cell cycle proteases that control the metaphase-to-anaphase transition by cleaving chromosomal cohesin rings. Two new high-resolution structures of separase bound by its inhibitory chaperone securin illustrate intriguing regulatory mechanisms.

SMC (structural maintenance of chromosomes) complexes are found in all living organisms and include condensin, cohesin and the SMC5–SMC6 complex. Recent mechanistic insight into these ring-shaped protein machines, which topologically encircle DNA, shed light on how they function to mediate chromosome condensation, sister chromatid cohesion and DNA repair.

The cohesin complex — best known for its role in cell division — does not rest between divisions, and instead participates in regulating gene expression. How it does this is only now becoming clear.

The eukaryotic cell cycle comprises an ordered series of events orchestrated by cyclin-dependent kinases (Cdks), with unidirectional cell-cycle transitions being required for its successful completion. Proteolytic degradation of cyclins has been assumed to be responsible for the irreversible transitions, but here it is shown that, although forced cyclin degradation can drive mitotic exit, the re-synthesis of cyclin means that this is not sufficient for irreversibility. Rather, mitotic exit only become irreversible after activation of a double-negative feedback loop.

In yeast, anaphase defects can trigger activation of the NoCut checkpoint, resulting in delayed cytokinesis. The Ilp1/aurora kinase localizes to the spindle midzone and monitors chromatin segregation, thus acting as a chromatin sensor.

The cohesin complex maintains genome integrity by ensuring correct sister-chromatid segregation during mitosis and meiosis. Here, Chaoet al. present a pseudo-atomic model of the full-length Scc2–Scc4 cohesin loader complex and reveal key Scc2 surfaces crucial for cohesin loading.

Chromosomes adopt their well-known form only at a certain phase in the cell-division cycle, just before they separate. But the proteins that help shape chromosomes also seem to be at work earlier on.

Chromosomal passenger proteins undergo spectacular changes in localization during cell division. We now have molecular insight into how and why these changes occur.

Anaphase onset is triggered when the protease separase cleaves the cohesive bond that holds replicated sister chromatids together until metaphase. In budding yeast, separase then also regulates mitotic exit. New findings suggest that in vertebrates, separase also participates in cell-cycle regulation, albeit in an unexpected manner.

The successful completion of mitosis requires that late mitotic events occur in a strict sequence. This is regulated, at least in part, by the order in which different cyclin-dependent kinase substrates are dephosphorylated and in which anaphase-promoting complex substrates are degraded.