Cell Cycle and Cell Division — Notes

All cells reproduce by dividing: a cell grows, duplicates its genome, synthesises other constituents and divides into two daughter cells. This sequence of events is the cell cycle. The duration varies with the organism and cell type: human cells in culture take about 24 hours, of which the M phase lasts only about 1 hour, whereas yeast completes a cycle in about 90 minutes.

The cycle has two parts. M phase (mitosis phase) is the actual division; interphase lies between two successive M phases and, in human cells, is more than 95 percent of the cycle (95.8 percent for the textbook figures). Interphase is a period of preparation, not a resting phase:

• G1 phase (gap 1): between the end of mitosis and the start of DNA replication; the cell is metabolically active and grows but does not replicate its DNA.
• S phase (synthesis): DNA replicates; the amount per cell doubles (from 2C to 4C) but the chromosome number remains the same (2n). In animal cells the centriole duplicates in the cytoplasm during S phase.
• G2 phase (gap 2): proteins are synthesised in preparation for mitosis, and cell growth continues.

Some cells do not divide further: they exit G1 and enter an inactive quiescent stage (G0). Cells in G0 remain metabolically active but do not proliferate unless called on to do so by the needs of the organism; many cells of the adult body, such as heart cells, stay in this stage, while others re-enter the cycle.

(The textbook figures of 24 hours and 90 minutes are typical values for cells in culture; real cycle times vary widely, and the phase lengths drawn in the diagrams are illustrative.)

Mitosis is the division in which a diploid parent cell gives two daughter cells with the same chromosome number, so it is called equational division. It is a continuous process, divided into karyokinesis (division of the nucleus) and cytokinesis (division of the cytoplasm), and karyokinesis is described in four stages.

• Prophase follows the S and G2 phases. Chromosomal material, which was a tangle of thin threads in interphase, condenses; each chromosome has two chromatids joined at the centromere. The centrosome, duplicated in S phase, begins to move to opposite poles and radiates microtubules, the asters; the two asters with the spindle fibres form the mitotic apparatus. By the end of prophase, the Golgi complex, endoplasmic reticulum, nucleolus and nuclear envelope disappear.
• Metaphase: the chromosomes are fully condensed and spindle fibres attach to the kinetochores (disc-shaped structures at the centromere). The chromosomes align at the equator, the metaphase plate; one chromatid of each chromosome is connected to a pole by spindle fibres, the other to the opposite pole. Metaphase is the best stage to count and study chromosome morphology.
• Anaphase: the centromeres split and the chromatids separate; each, now a chromosome, moves to the opposite pole, centromere first.
• Telophase: the chromosomes reach the poles and decondense; the nuclear envelope reforms around each group, and the nucleolus, Golgi complex and ER reform.

Cytokinesis follows. In an animal cell a furrow appears in the plasma membrane and deepens until the cell is divided. In a plant cell, which has a rigid wall, a cell plate forms in the centre and grows outwards to meet the side walls; it represents the middle lamella between the new cells, and the cell wall materials are then laid down on it. Sometimes karyokinesis is not followed by cytokinesis, giving multinucleate cells (syncytium), as in the liquid endosperm of coconut.

Significance: daughter cells are genetically identical to the parent, so mitosis maintains the genetic make-up. It is responsible for growth (the zygote becomes a multicellular body), it restores the nucleo-cytoplasmic ratio when a growing cell becomes too large for its nucleus, it replaces and repairs cells (skin, intestinal lining) and, in plants, it enables the meristems to add new cells throughout life.

Counting: a diploid cell with 2n = 8 has 8 chromosomes (16 chromatids) at metaphase; at anaphase, once the centromeres split, the whole cell holds 16 chromosomes, and each daughter nucleus ends up with 8. The mitotic index is the percentage of cells in division in a sample, and in a population with cells at all stages the share of cells in a stage is proportional to the time spent in it.

Meiosis is the specialised division that produces haploid gametes from diploid meiocytes (gamete mother cells) so that the chromosome number stays constant across generations. It involves two sequential cycles of nuclear and cell division, meiosis I and meiosis II, but only a single cycle of DNA replication. Meiosis I is initiated after the parental chromosomes have replicated to produce identical sister chromatids at the S phase. Meiosis I is the reduction division; meiosis II is equational. Four haploid cells result.

Meiosis I — prophase I is prolonged and has five substages.

• Leptotene: chromosomes gradually become visible under the light microscope; compaction continues.
• Zygotene: homologous chromosomes start pairing and aligning (synapsis), aided by the synaptonemal complex. The paired chromosomes are called bivalents or tetrads.
• Pachytene: the bivalents clearly appear as tetrads of four chromatids. Crossing over, the exchange of segments between non-sister chromatids of homologous chromosomes, occurs at recombination nodules, and is catalysed by the enzyme recombinase.
• Diplotene: dissolution of the synaptonemal complex; the recombined homologous chromosomes separate except at the sites of crossovers, the X-shaped chiasmata. In oocytes of some vertebrates diplotene can last for months or years.
• Diakinesis: terminalisation of chiasmata; chromosomes are fully condensed and the meiotic spindle is assembled; the nucleolus disappears and the nuclear envelope breaks down, marking the end of prophase I.

Metaphase I: the bivalents align on the equatorial plate; microtubules from opposite poles attach to the kinetochores of the homologous chromosomes. Anaphase I: the homologous chromosomes separate, while sister chromatids remain associated at their centromeres. Telophase I: the nuclear membrane and nucleolus reappear; cytokinesis follows and the product is a dyad of cells. The stage between the two meiotic divisions is interkinesis; it is generally short-lived and no DNA replication occurs.

Meiosis II — prophase II: the nuclear membrane disappears and the chromosomes become compact again. Metaphase II: the chromosomes align at the equator, and the kinetochores of sister chromatids attach to spindle fibres from opposite poles. Anaphase II: the centromere splits and the chromatids move to opposite poles. Telophase II: two groups of chromosomes are enclosed by nuclear envelopes; cytokinesis gives a tetrad of four haploid cells.

Counting. For 2n = 14: there are 7 bivalents; a cell of the dyad has 7 chromosomes of two chromatids each; at anaphase II each cell momentarily has 14 chromosomes; each final cell has 7. If the G1 nucleus has 9.6 pg of DNA, it has 19.2 pg after S, 9.6 pg per cell after meiosis I (half the chromosomes, still two chromatids each) and 4.8 pg after meiosis II.

Significance: meiosis conserves the chromosome number from generation to generation in sexually reproducing organisms (fusion of two haploid gametes restores the diploid number), and it increases genetic variability through crossing over and the separation of homologues; variations are very important for evolution.