(see Figure 2.12b). Ironically, active MPF brings about its own demise by destroying cyclin. In brief, high levels of active MPF stimulate mitosis, and low levels of MPF bring a return to interphase conditions.

A number of factors stimulate the synthesis of cyclin B and the activation of MPF, whereas other factors inhibit MPF. Together these factors determine whether the cell passes through the G2/M checkpoint and ensure that mitosis is not initiated until conditions are appropriate for cell division. For example, DNA damage inhibits the activation of MPF; the cell is arrested in G2 and does not undergo division.

The Gj/S checkpoint is regulated in a similar manner. In fission yeast (Shizosaccharomyces pombe), the same CDK is used, but it combines with Gj cyclins. Again, the level of CDK remains relatively constant, whereas the level of Gj cyclins increases throughout Gj. When the activated CDK-G1-cy-clin complex reaches a critical concentration, proteins necessary for replication are activated and the cell enters S phase.

Many cancers are caused by defects in the cell cycle's regulatory machinery. For example, mutation in the gene that encodes cyclin D, which has a role in the human G1/S checkpoint, contributes to the rise of B-cell lymphoma. The overexpression of this gene is associated with both breast and esophageal cancer. Likewise, the tumor-suppressor gene p53, which is mutated in about 75% of all colon cancers, regulates a potent inhibitor of CDK activity. __

Concepts B

The cell cycle produces two genetically identical cells, with no net change in chromosome number. Progression through the cell cycle is controlled at checkpoints, which are regulated by interactions between cyclins and cyclin-dependent kinases.

Connecting Concepts 9

Counting Chromosomes and DNA Molecules

The relations among chromosomes, chromatids, and DNA molecules frequently cause confusion. At certain times, chromosomes are unreplicated; at other times, each possesses two chromatids (see Figure 2.7b). Chromosomes sometimes consist of a single DNA molecule; at other times, they consist of two DNA molecules. How can we keep track of the number of these structures in the cell cycle?

There are two simple rules for counting chromosomes and DNA molecules: (1) to determine the number of chromosomes, count the number of functional centromeres; (2) to determine the number of DNA molecules, count the number of chromatids. Let's examine a hypothetical cell as it passes through the cell cycle ( FIGURE 2.13). At the beginning of G1, this diploid cell has a complete set of four chromosomes, inherited from its parent cell. Each chromosome consists of a single chromatid — a single DNA molecule — so there are four DNA molecules in the cell during G1. In S phase, each DNA molecule is copied. The two resulting DNA molecules combine with histones and other proteins to form sister chromatids. Although the amount of DNA doubles during S phase, the number of chromosomes remains the same, because the two sister chromatids share a single functional centromere. At the end of S phase, this cell still contains four chromosomes, each with two chromatids; so there are eight DNA molecules present.

Through prophase, prometaphase, and metaphase, the cell has four chromosomes and eight DNA molecules. At anaphase, however, the sister chromatids separate. Each now has its own functional centromere, and so each is considered a separate chromosome. Until cytokinesis, each cell contains eight chromosomes, each consisting of a single chromatid;

Number of chromosomes per cell

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