Figure: Caption: The cell cycle is controlled at several checkpoints, including one at the G2/M transition, and another in late G1 phase before.

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Figure: 23-01 Caption: The cell cycle is controlled at several checkpoints, including one at the G2/M transition, and another in late G1 phase before entry into S phase. These checkpoints involve the interaction between transitory proteins, called cyclins, and kinases that add phosphate groups to proteins. Phosphorylation of target proteins triggers a cascade of events allowing progress through the cell cycle.

Figure: 23-04 Caption: (a) In familial retinoblastoma, one mutation is inherited and present in all cells. A second mutation at the retinoblastoma locus in any retinal cell will result in uncontrolled cell growth and tumor formation. (b) In spontaneous retinoblastoma, two mutations in the retinoblastoma gene in a single cell are acquired sequentially, causing uncontrolled cell growth and division, and resulting in tumor formation.

Figure: 23-07 Caption: DNA damage activates the kinase ATM, and/or the kinase Chk2. Once activated, these kinases stimulate the phosphorylation of the nuclear proteins p53 and BRCA1. Phosphorylation stabilizes p53, leading to increased levels of the protein. As the concentration of p53 increases, it activates a cell cycle control point, halting DNA replication. The phosphorylated BRCA1 protein interacts with a number of other proteins, including BRCA2 and mRAD51 to bring about repair of double-stranded DNA breaks by homologous recombination.

Figure: 23-12 Caption: A model for the multistep production of colon cancer. The first step is the loss or inactivation of one allele of the APC gene on chromosome 5. In familial cases, one mutation of the APC gene is inherited. Subsequent mutations involving genes on chromosomes 12, 17, and 18 in cells of the benign adenomas can lead to a malignant transformation resulting in colon cancer. Although the mutations in chromosomes 12, 17, and 18 usually occur at a later stage than those involving chromosome 5, the sum of the changes is more important than the order in which they occur.

Marx, J. (2002) Science 297: 544-546