Cell Cycle

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During the cell cycle, cells grow, double their nuclear deoxyribonucleic acid (DNA) content through chromosome replication, and prepare for the next mitosis (chromosome separation) and cytokinesis (cytoplasm separation). In effect, the cell cycle is the proliferating cell's life history. Cells spend most of their time in interphase, the period between divisions, acquiring competence for division. For example, in the higher plant Arabidopsis thaliana at23°C, meristematic cells are in interphase for eight hours but are in mitosis for only thirty minutes.

An idealized cell cycle, showing the order of mitosis (M), cytokinesis (C), postmitotic interphase (G1), DNA synthetic phase (S-phase), and postsynthetic interphase (G2). Major control points of the cell cycle at G1/S and G2/M are indicated as hatched rectangles. P34 (Cdc2 kinase) is shown bound to a cyclin at G2/M, where it exhibits catalytic activity (ﾀ) while cyclin degrades at M/G1 and Cdc2 stops working (X). A Cdc2-cylin complex is also shown at G1/S, but note this is not necessarily the same cyclin as the one at G2/M.

The cell cycle is commonly described as having four phases: M (mitosis), Gap 1 (postmitotic interphase), S-phase (period of DNA synthesis), and Gap 2 (postsynthetic interphase). Gaps 1 and 2 were initially thought to be resting stages between mitosis and S-phase. This description is a misnomer because numerous genes regulate cell growth in these phases. Appropriately, these terms became abbreviated to G1 and G2. Moreover, networks of cell cycle gene products constitute molecular checkpoints that in G1 determine whether a cell is competent to replicate its chromosomes during S-phase, and that in G2 sense whether the cell is ready to partition its chromatids during mitosis. Uniquely in plant cells, in late G2 an array of microtubules known as the preprophase band appears and chromosomes separate in a plane perpendicular to it.

Only in mitosis do chromosomes become visible by light microscopy; each one appears as two sister chromatids constricted at a specific point along their length, the centromere. At mitosis, a diploid parent cell passes through four phases: prophase, metaphase, anaphase, and telophase. During late prophase, the nuclear envelope disintegrates and spindles of microtubules span the cell. Unlike animal mitosis where the spindles attach to centrioles (and associated polar asters), there is no obvious anchoring structure for higher plant spindles. This led to the botanical term "anastral cell division." At metaphase, the chromosomes align at the cell's equator and attach to mitotic spindles via kinetochores, discs of structural protein that alsobind to the centromere of the chromosome. During anaphase, sister chromatids are pulled apart and move to opposite ends of the cell. In telophase, nuclear envelopes reform around each new diploid set of chromosomes followed by cytokinesis when a new wall forms between sibling cells. Cytokinesis requires the formation of a cell plate or phragmoplast that spans the cell center, and becomes dense with vesicles from the Golgi complex (also called the Golgi apparatus). The plasma membrane and the membrane surrounding the phragmoplast fuse, resulting in separation of the sibling cells. On the phragmoplast, cellulose forms the fibrillar component of the cell wall while hemicelluloses and pectins are added as a matrix. Trapped in the primary cell wall are cytoplasmic strands and microtubules that become plasmodesmata, the cytoplasmic connections between the new cells.

Arrows point to a developing cell plate, which divides the new daughter cells.

Most knowledge about regulatory cell cycle genes comes from studies of yeasts and vertebrate cells, but the molecular landscape of the plant cell cycle is being identified. In fact, an important discovery about the cell cycle stemmed from work on plant cells in the 1960s by Jack Van't Hof at the Brookhaven National Laboratory in New York. He discovered that when cultured pea root tips were deprived of carbohydrate, meristematic cells stopped dividing and arrested in either G1 or G2. If sucrose and inhibitors of protein synthesis or adenosine triphosphate (ATP) synthesis were then added to the medium, the cells continued to arrest in G1 or G2 despite nutrient availability. With confirmatory data from other species, in 1973 Van't Hof published his principal control point hypothesis: that there are two major control points of the cell cycle, one at G1/S and the other at G2/M, both of which are dependent on adequate nutrients, the generation of energy, and protein synthesis. Discovery of the proteins synthesized at these transitions and the genes that encode them occurred in the 1980s. Paul Nurse at the Imperial Cancer Research Fund (ICRF) in London discovered that a fission yeast cell division cycle (cdc) gene, cdc2, was absolutely requiredfor the G2/M and G1/S transitions. Cdc2 encodes a protein kinase, an enzyme that catalyzes substrate phosphorylation. Although the kinase (also called p34 because its molecular weight is 34 kilodaltons), is not fully understood, it can phosphorylate lamin proteins that line the inside of the nuclear envelope. Notably, phosphorylated lamins become unstable, leading to nuclear envelope breakdown. Presumably, p34 drives a cell into mitosis at least partly because it phosphorylates lamins. Genes equivalent to cdc2 have been discovered in humans, frogs, insects, fish, and higher plants.

How does mitosis stop so abruptly when two siblings enter G1, even though p34 is still present? This puzzle was partly solved by Tim Hunt at the ICRF laboratories. A protein extract injected into immature frog oocytes caused them to undergo meiosis prematurely. Hunt noticed one protein in the extract that increased in concentration during the cell cycle but disappeared suddenly at the M to G1 phase transition. It was called cyclin. Data from the fission yeast and frog systems indicated that p34 depends on cyclin for its phosphorylating activity. In fact, p34 and cyclin bind together from late G2 until late mitosis and then, suddenly, cyclin is degraded, p34 stops working, and mitosis ends. Plant-like cyclins have also been identified in various higher plants including Arabidopsis, alfalfa, and rice, reflecting remarkable conservation of the key cell cycle genes among unrelated organisms.

Cells; Cells, Specialized Types; Meristems.

Alberts, Bruce, D. Bray, J. Lewis, M. Raff, K. Roberts, and J. D. Watson. The Molecular Biology of the Cell, 3rd ed. New York: Garland, 1994.