Checkpoint genes in cancer

The mammalian cell cycle is exquisitely controlled by a 'machinery' compose d of cyclin-dependent kinases and their binding partners. the cyclins, Thes e kinases regulate transitions into DNA synthesis and mitosis, and their in activity contributes to cellular quiescence, differentiation and senescence . Cell cycle transitions are, in turn, controlled by checkpoints that monit or ribonucleotide pools, oxygen tension, the extracellular environment, gro wth signalling programmes. the status of DNA replication. and the mitotic s pindle apparatus. Genes positively controlling cell cycle checkpoints can b e targets for oncogenic activation in cancer, whereas negative regulators, such as tumour suppressor genes, are targeted for inactivation. Understandi ng the molecular details of cell cycle regulation and checkpoint abnormalit ies in cancer offers insight into potential therapeutic strategies.