The complex mechanisms that regulate the eukaryotic cell cycle are prime targets for oncogenic mutations. Both positively and negatively acting proteins precisely control the entry of cells into the cell cycle and their progression through it. In addition, cells harbor surveillance mechanisms—known as checkpoint pathways—that ensure that cells do not enter the next phase of the cell cycle before the previous one has been correctly completed. For example, cells that have sustained damage to their DNA are normally arrested before their DNA is replicated, or in G₂ before chromosome segregation. This arrest of the cell cycle allows time for the DNA damage to be repaired; alternatively, cells are directed to commit suicide via apoptosis. The cell cycle control and checkpoint systems function to prevent cells from becoming cancerous. As might be expected, mutations in this system often lead to abnormal development or contribute to cancer.

In this section, we discuss the cell cycle checkpoint pathways that are affected in cancer. We first describe how the checkpoint pathway that controls entry into the cell cycle is mutated and misregulated in most human cancers. We then discuss how p53 prevents tumorigenesis by helping cells to respond to DNA damage. We end with a discussion of how defects in DNA repair enzymes contribute to cancer by compromising the cell’s ability to repair DNA damage.

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