DNA replication, mitotic spindle formation, chromosome segregation and cytokinesis must be carefully controlled to ensure that all genetic information is passed over to the next cell generation. Although the core cell cycle machinery has been worked out, and the cyclin-dependent kinases and cyclins entered the textbooks a long time ago, we still lack a complete understanding of how events of the cell cycle are executed and coordinated. In mitosis, the microtubule-based spindle organizes duplicated chromosomes to allow the segregation of two identical sets to daughter cells. In most cells, centrosomes, each consisting of two centrioles, are the main organizers of microtubules, influencing spindle assembly and chromosome segregation. Centrosomes, like chromosomes, need to be replicated only once per cell cycle and segregated when the cell divides. Erich Nigg and Tim Stearns discuss recent insights into the centrosome life cycle, the potential role of centrosomes in genomic stability and aspects of asymmetry in centriole architecture and segregation. Before separation occurs in anaphase, however, duplicated sister chromatids are held tightly together. The 'DNA glue' is provided by the cohesin complex, vital also for cohesion during DNA repair and replication. Mechanistically, cohesin has been suggested to form a ring that entraps the DNA, but the precise structure of the ring, and how it would come on and off DNA remains a mystery. Kim Nasmyth describes findings on cohesin function and proposes a model to explain cohesin loading onto — and dissociation from — DNA.

Another aspect of cell cycle progression is the existence of safeguarding mechanisms called 'checkpoints' that ensure everything is in order before allowing the next event to proceed. The spindle checkpoint (or spindle assembly checkpoint, SAC) monitors the alignment of the full set of chromosomes on the mitotic spindle before anaphase can take place. In the twenty years since the isolation of the first spindle checkpoint genes in yeast, much has been learned about the molecular players in the SAC. In a Historical Perspective, Andrew Murray discusses these advances and outlines the most important questions that remain to be resolved.

Repairing damaged DNA is crucial for genomic stability. Recent research has revealed that chromatin undergoes dramatic changes in response to DNA damage. This causes a massive accumulation of proteins in 'nuclear foci'. Jiri Lukas, Claudia Lukas and Jiri Bartek review the numerous post-translational modifications of chromatin proteins following DNA damage, and their potential biological function.

In addition to these articles, an accompanying online library on this topic presents selected research papers and reviews from Nature journals. We thank our authors and reviewers for their contributions and hope that our readers will share our enthusiasm for this Focus issue.