Publication highlights

Researchers at the Crick have shown that the 'pacemaker' controlling yeast cell division lies inside the nucleus rather than outside it, as previously thought. They developed sensors to look inside single live yeast cells to monitor the activity of cyclin-dependent kinase (CDK), the master regulator of the cell cycle. The sensor in the nucleus reported a peak in activity before the sensor in the cytoplasm. They also found that some cyclin-CDK complexes (the active form of CDK) were being exported from the nucleus to kickstart mitosis in the cytoplasm. Finally, they found that the nucleus needed a higher amount of cyclin to enter mitosis but could then tolerate decreases in cyclin without slipping out of mitosis, unlike in the cytoplasm. This is likely to allow cell division to be coupled to the mechanism for monitoring DNA replication and damage, preventing mitosis from happening when the DNA is not 'ready'.

Researchers at the Crick studied the location of the protein complex cyclin-CDK, the master regulator of cell division, within the cell, specifically at an organelle (a structure in the cell) called the centrosome. Although it has long been known that cyclin-CDK is concentrated at the centrosome, the importance of this localisation was unclear. Using fission yeast as a simple model organism, they studied a mutant form of cyclin-CDK that did not localise to the centrosome, and also could not drive cell division. They found that artificially tethering the mutant cyclin-CDK back to the centrosome, to mimic its normal localisation, largely restored its ability to drive cell division. This showed that cyclin-CDK localisation to the centrosome is essential for mitosis in yeast, and highlights the importance of the spatial regulation of cyclin-CDK.

Research from the Cell Cycle Laboratory has shown that the rate of protein synthesis in living cells is far more variable than first thought. The researchers fed yeast cells with different amino acids in regular intervals, measuring the rat each amino acid was incorporated into proteins. They found that the variability in the rate of protein synthesis was not caused by cell size and stage in the cell cycle and changed within 20-30 minutes in one cell. They also found that the level of variability increased or decreased depending on different mutations in the TOR pathway, suggesting that variability is genetically controlled and confer an evolutionary advantage.

The organisational principles of the eukaryotic cell cycle have previously been put down to two opposing models of enzyme activity. Researchers in the Nurse Lab have developed proteomics assays that allow them to monitor the levels of enzymes in yeast that control the cell cycle. They found that the cell cycle is controlled through a hybrid of both models, although the contribution of one strongly outweighs the other. It is likely that these findings in yeast reflect core control principles shared by eukaryotes.

Researchers in the Parker lab have unpicked the action of protein kinase C (PKC) in modulating cell growth and division. The team developed a novel trap for proteins regulated by PKC by engineering UV-photocrosslinkable amino acids into PKCε to produce a sort of molecular flypaper. They captured a previously unknown PKCε target, the RNA-binding protein SERBP1, and showed that SERBP1 was required for successful chromosome segregation and cell division. Their work provides a new insight into how cells protect their genome during division and also which regulatory processes could play a key role when cells become cancerous.

Disruption of a hydrophobic patch in the Cdc13 B-cyclin prevents localisation of CDK at the centrosomal spindle pole body, blocks mitosis, and compromises phosphorylation of the weakest CDK substrates. We propose this mechanism contributes to CDK substrate regulation.