Mitogen-dependent progression through the first gap phase (G1) of the mammalian celldivision
cycle is precisely regulated so that normal cell division is coordinated with cell
growth, while the initiation of DNA synthesis (S phase) is precisely ordered to prevent
inappropriate amplification of the DNA that may cause genome instability. To ensure that
these fundamental requirements of cell division are met, cells have developed a surveillance
mechanism based on an intricate network of protein kinase signaling pathways that lead to
several different types of checkpoints. Since these checkpoints are central to the maintenance
of the genomic integrity and basic viability of the cells, defects in these pathways
may result in either tumorigenesis or apoptosis, depending on the severity and nature of the
defects. This review summarizes the genetic and molecular mechanisms of checkpoint activation
in the G1/S and S phases of the mammalian cell cycle that monitor DNA damage and
replication. The relevance of these mechanisms to the origin of cancer is also discussed.