Question

Mammalian cells face a variety of choices as they proceed through the restriction point of the cell cycle. What are these choices and what happens if the cells remain in the cell cycle? What happens if they exit the cell cycle? How do these mechanisms work?

Answer 1

Several cell cycle checkpoints function to ensure that incomplete or damagedchromosomes are not replicated and passed on to daughter cells. One of the most clearly defined of these checkpoints occurs in G2 and prevents the initiation of mitosis until DNA replication is completed. This G2 checkpoint senses unreplicated DNA, which generates a signal that leads to cell cycle arrest. Operation of the G2 checkpoint therefore prevents the initiation of M phase before completion of S phase, so cells remain in G2 until the genome has been completely replicated. Only then is the inhibition of G2progression relieved, allowing the cell to initiate mitosis and distribute the completely replicated chromosomes to daughter cells.

Progression through the cell cycle is also arrested at the G2 checkpoint in response to DNA damage, such as that resulting from irradiation.

DNA damage not only arrests the cell cycle in G2, but also slows the progression of cells through S phase and arrests cell cycle progression at a checkpoint in G1.

In mammalian cells, arrest at the G1 checkpoint is mediated by the action of a protein known as p53, which is rapidly induced in response to damaged DNA (Figure 14.9). Interestingly, the geneencoding p53 is frequently mutated in human cancers.