Chapter 23

## Abstract

Abstract  The process of cell reproduction is known as the cell cycle.13 Usually the cell cycle produces two progeny, or daughter cells, that closely resemble their parent and who are themselves capable of repeating the process. For this to occur, three things are necessary: replication of the genome; a doubling of cell mass (where cell mass refers generally to all cellular components other than chromosomes); and a precise segregation of chromosomes plus a more or less equal distribution of other cell components to the daughter cells. The execution of these events divides the cell cycle into four phases: chromosomes are replicated during S (synthetic) phase; cell constituents are segregated to daughter cells during M (mitotic) phase; and two G (gap) phases intervene between S and M. G1 precedes S phase, and G2 precedes mitosis (Fig. 23-1). Thus, chromosome replication and segregation are confined to discrete intervals of the cell cycle, whereas the third essential component of cell reproduction—growth—occurs continuously in G1, S, G2, and M. It is during G1 and G2 that cells typically respond to the proliferative and antiproliferative signals that determine whether the cell cycle ought to proceed (signals such as growth factors and cytokines). In this way, the cell cycle has the option of stopping within G1 and G2 without interrupting the critical and precarious events of chromosome replication and chromosome segregation.

Fig. 23-1

The four phases of the cell cycle. Interphase is composed of S (synthesis) phase, during which time DNA replication occurs, and two G (gap) phases, during which cells respond to various proliferative and antiproliferative stimuli and cell growth occurs. Chromosomes and cellular contents are than distributed to two daughter cells during M (mitosis) phase, and the resulting progeny re-enter the cell cycle in G1.

Abstract  Faithful reproduction of the cell requires that these events be coordinated with one another. Thus, mitosis ordinarily waits until all chromosomes have been replicated and the cell has doubled in size. However, there are specialized cell cycles where these processes are uncoupled from one another (Fig. 23-2). Repeated S phases with no intervening M phases, known as endocycles, result in the increased chromosome ploidy that is seen in megakaryocytes. Conversely, the basic cell-cycle logic of meiosis is the execution of two sequential M phases without an S phase. A third important variation is seen in the cleavage cycles that occur after fertilization of amphibian eggs. Amphibian eggs are huge cells, which, after fertilization, undergo extremely rapid cell cycles consisting of alternating S and M phases with no cell growth. After approximately 12 cleavage cycles, the embryo consists of 4000 cells, each containing a full complement of genetic material, and each now reduced to the size of a typical somatic cell.4, 5

Fig. 23-2

Specialized cell cycles. A, A normal cell cycle is depicted in which a cell gives rise to two identical daughter cells. B, During megakaryopoiesis, promegakaryocytes undergo repeated rounds of DNA replication in the absence of mitosis (endoreduplication), resulting in polyploid megakaryocytes with a DNA content greater than their progenitors. C, In meiosis, two successive cell divisions after DNA replication result in four haploid daughter cells. D, Amphibian eggs undergo 12 rapid cell cycles consisting of alternating S and M phases. No cell growth occurs during these cycles, and the large egg cell is subdivided into approximately 4000 cells, each containing a normal complement of chromosomes.

Abstract  These simple examples show that each of the component processes of the cell cycle—growth, chromosome replication, and mitosis—can occur independently of the others. Because cell reproduction could not occur if these processes were executed in random order, there need to be mechanisms for establishing and enforcing the normal sequence of events. This chapter describes the molecules that control progression through the cell cycle, and illustrates how their activities are linked together to orchestrate the orderly process of cell reproduction. Based on these ideas, we suggest that cancer may be a disease of the cell cycle, a hypothesis that is elaborated on in subsequent chapters.

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