DNA replication and damage checkpoints and meiotic cell cycle controls in the fission and budding yeasts

The cell cycle checkpoint mechanisms ensure the order of cell cycle events to preserve genomic integrity. Among these, the DNA-replication and DNA-dam age checkpoints prevent chromosome segregation when DNA replication is inhi bited or DNA is damaged. Recent studies have identified an outline of the r egulatory networks for both of these controls, which apparently operate in all eukaryotes. In addition, it appears that these checkpoints have two arr est points, one is just before entry into mitosis and the Other is prior to chromosome separation. The former point requires the central cell-cycle re gulator Cdc2 kinase, whereas the latter involves several key regulators and substrates of the ubiquitin ligase called the anaphase promoting complex. Linkages between these cell-cycle regulators and several key checkpoint pro teins are beginning to emerge. Recent findings on post-translational modifi cations and protein-protein interactions of the checkpoint proteins provide new insights into the checkpoint responses, although the functional signif icance of these biochemical properties often remains unclear. We have revie wed the molecular mechanisms acting at the DNA-replication and DNA-damage c heckpoints in the fission yeast Schizosaccharomyces pombe, and the modifica tions of these controls during the meiotic cell cycle. We have made compari sons with the controls in fission yeast and other organisms, mainly the dis tantly related budding yeast.