Key Concepts Of Section 216

Cell-Cycle Control in Mammalian Cells

■ Various polypeptide growth factors called mitogens stimulate cultured mammalian cells to proliferate by inducing expression of early-response genes. Many of these encode transcription factors that stimulate expression of delayed-response genes encoding the G1 CDKs, G 1 cyclins, and E2F transcription factors.

■ Once cells pass the restriction point, they can enter the S phase and complete S, G2, and mitosis in the absence of growth factors.

21.7 Checkpoints in Cell-Cycle Regulation

Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. For example, when S-phase cells are induced to enter mitosis by fusion to a cell in mitosis, the MPF present in the mitotic cell forces the chromosomes of the S-phase cell to condense. However, since the replicating chromosomes are fragmented by the condensation process, such premature entry into mitosis is disastrous for a cell.

Another example concerns attachment of kineto-chores to microtubules of the mitotic spindle during metaphase. If anaphase is initiated before both kine-tochores of a replicated chromosome become attached to micro-tubules from opposite spindle poles, daughter cells are produced that have a missing or extra chromosome (Figure 21-31). When this process, called nondisjunction, occurs during the meiotic division that generates a human egg, Down syndrome can occur from trisomy of chromosome 21, resulting in developmental abnormalities and mental retardation. I

To minimize the occurrence of such mistakes in cell-cycle events, a cell's progress through the cycle is monitored at several checkpoints (Figure 21-32). Control mechanisms that operate at these checkpoints ensure that chromosomes are intact and that each stage of the cell cycle is completed before the following stage is initiated. Our understanding of these control mechanisms at the molecular level has advanced considerably in recent years.

^ Anaphase

^ Anaphase

Missing Extra chromosome chromosome

Missing Extra chromosome chromosome

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