DNA STRUCTURE-DEPENDENT CHECKPOINTS IN MODEL SYSTEMS

DNA structure dependent checkpoints require a number of proteins which function to arrest the cell cycle in response to DNA damage (such as UV induced lesions) or blocks to DNA replication. Analogous to a signa l transduction pathway, checkpoints communicate information between a DNA lesion and the cell cycle machinery. This brief review will focus on yeast model systems which have been instrumental in identifying the various components (initiating signal, detection, signal transduction and cell cycle effector) of the checkpoint pathways. The biological s ignificance of these pathways in mammalian cells is illustrated in pat ients with ataxia telangiectasia (AT), a multi-system cancer-prone dis order in which DNA damage checkpoints affecting both DNA replication a nd mitosis are lost. ATM, the gene mutated in this disorder is structu rally related to the yeast rad3/MEC1 checkpoint genes. This demonstrat es the high degree of evolutionary conservation of checkpoints amongst eukaryotic organisms.