Control of the G2/M transition

The G, checkpoint prevents cells from entering mitosis when DNA is damaged, providing an opportunity for repair and stopping the proliferation of damaged cells. Because the G(2) checkpoint helps to maintain genomic stability, it is an important focus in understanding the molecular causes of cancer, Many different methods have been used to investigate the G, checkpoint and uncover some of the underlying mechanisms. Because cell cycle controls are highly conserved, a remarkable synergy between the genetic power of model organisms and biochemical analyses is possible and has uncovered control mechanisms that operate in many diverse species, including humans. CDC2, the cyclin-dependent kinase that normally drives cells into mitosis, is the ultimate target of pathways that mediate rapid arrest in G(2) in response to DNA damage. Additional pathways ensure that the arrest is stably maintained. When mammalian cells contain damaged DNA, the p53 tumor suppressor and the Rb family of transcriptional repressors work together to downregulate a large number of genes that encode proteins required for G(2) and M. Elimination of these essential cell cycle proteins helps to keep the cells arrested in G(2).