ABSTRACT
Eukaryotic cells can respond to an attack by DNA-damaging agents with arrest in various stages of the cell cycle. Such checkpoint responses are transient, actively regulated and beneficial to the organism (1,2). It is thought that transient arrest creates enhanced opportunities for DNA repair and prevents the conversion of repairable into irreparable damage, such as mutations or chromosome fragmentation, by processes, such as mitosis, that are associated with cell cycle progression. It is instructive to discuss a checkpoint process as an example of a signal-transduction pathway-with sensors that recognize DNA damage or a consequence of DNA damage, mediators that amplify and transform the signal into activation of transducers and executers that finally modify cell cycle targets. Coordinated and related responses use a largely overlapping signal-transduction network: these include decisions on cell fate (such as apoptosis or senescence), transcriptional regulation of genes involved in DNA repair and direct modification of repair proteins. Indeed, it has been argued that regulation of repair may be of more importance for resistance to DNA-damaging agents than cell cycle arrest. Failure to invoke these signal-transduction networks can give rise to genetic instability and this area of investigation has considerable ramifications for cancer research. However, a conceptually similar signal-transduction system appears to exist already in Escherichia coli, as mentioned in the previous chapter.
