Cell Division: Mitosis and Meiosis

A dividing cell goes through a repeating sequence called the cell cycle. Most of it is interphase, when the cell grows and copies its DNA. Interphase has three parts: G1, when the cell grows and does its normal work; S (synthesis), when every chromosome is copied; and G2, when the cell prepares to divide. Then comes the mitotic phase, M: mitosis divides the nucleus, and cytokinesis divides the rest of the cell (see OpenStax Biology 10.2).

Not every cell keeps cycling. Cells can leave G1 for a resting state called G0. Some come back when signaled; others, such as many nerve cells and heart muscle cells, stay in G0 for life (see OpenStax Biology 10.3).

What pushes a cell past a checkpoint? Proteins called cyclins rise and fall in amount through the cycle. A cyclin switches on a partner enzyme, a cyclin-dependent kinase (Cdk). The active Cdk-cyclin pair adds phosphate groups to other proteins, changing their shape and activity in ways that move the cell into the next phase. When the cyclin is broken down, the Cdk switches off again (see OpenStax Biology 10.3).

After S phase, each chromosome is two identical sister chromatids joined at the centromere. Mitosis gives one chromatid of every chromosome to each new nucleus. It is usually split into five phases: prophase, prometaphase, metaphase, anaphase and telophase (see OpenStax Biology 10.2). Some books fold prometaphase into prophase.

Counting gets tricky because the word "chromosome" counts centromeres. Two sister chromatids joined together are one chromosome; once they separate in anaphase, each is a chromosome of its own. The stepper below tracks a model cell with just 4 chromosomes (2n = 4) so you can follow every count. DNA per cell is given in units of c, the amount in one set of chromosomes, so a normal body cell in G1 has 2c.

Cytokinesis usually starts in late anaphase or telophase. In animal cells, a ring of actin filaments just inside the membrane contracts at the middle of the cell, pulling it inward to make a cleavage furrow that deepens until the cell pinches in two. Plant cells have a rigid wall and cannot pinch. Instead, vesicles from the Golgi apparatus gather at the middle and fuse into a cell plate, which grows outward until it joins the side walls and becomes a new wall between the two cells (see OpenStax Biology 10.2).

If eggs and sperm had 46 chromosomes each, a fertilized egg would have 92. Meiosis avoids this by dividing twice after a single round of copying, so each of the four cells it makes gets one chromosome from every pair: 23 in humans. A cell with two sets is diploid (2n); one with a single set is haploid (n).

The two chromosomes of a pair are homologous chromosomes, or homologs: one from your mother, one from your father, carrying the same genes in the same order, though often different versions (alleles) of them. In prophase I, homologs pair up tightly along their length, called synapsis. Each pair now has four chromatids, sometimes called a tetrad. Non-sister chromatids then swap matching segments, called crossing over; the points where they crossed show up as X-shaped chiasmata (singular chiasma) (see OpenStax Biology 11.1).

In meiosis I the homologs separate, halving the chromosome number. In meiosis II the sister chromatids separate, much as in mitosis. Which way each pair faces at metaphase I is random and independent of the other pairs, called independent assortment. With 23 pairs, that alone gives 2²³, over eight million, possible combinations of chromosomes in a gamete, before crossing over adds more (see OpenStax Biology 11.1). Switch the stepper above to Meiosis to follow the counts.

Sometimes a pair of homologs, or a pair of sister chromatids, fails to separate during meiosis. This is nondisjunction. One gamete gets an extra copy of a chromosome and another gets none. If a gamete with two copies of chromosome 21 is fertilized, the embryo has three: trisomy 21, the cause of Down syndrome. The chance of nondisjunction rises with the age of the person whose eggs are involved (see OpenStax Biology 13.2).

In a healthy body, new cells are balanced by cells that die on purpose, a process called apoptosis. Cancer begins when a cell escapes the controls on the cell cycle and keeps dividing, passing its faults on to its daughter cells (see OpenStax Biology 10.4). Two kinds of genes matter most.

Proto-oncogenes code for the positive regulators that move the cycle forward, such as Cdks and the receptors for growth signals. Normally they act only when the cell receives the right signal. A mutation can make one of these proteins active all the time, for example a Cdk that works without its cyclin. The mutated gene is then an oncogene, and it keeps pushing the cell past checkpoints it should not pass, like a car's accelerator stuck to the floor (see OpenStax Biology 10.4).

Tumor suppressor genes code for the brakes. Rb holds a cell at the G1 checkpoint: while active, it binds a protein called E2F that is needed to switch on the genes for S phase. As the cell grows, Rb gets phosphorylated, lets go of E2F, and the cell moves on. p53 responds to DNA damage: it halts the cycle so the damage can be repaired and, if the DNA cannot be fixed, it triggers apoptosis (see OpenStax Biology 10.3). If these brakes are lost, a cell with damaged DNA keeps dividing. Mutated p53 has been found in more than half of all human tumors (see OpenStax Biology 10.4). Usually several mutations, in both kinds of gene, build up before a cell becomes cancerous.

Henrietta Lacks and HeLa cells

In 1951, Henrietta Lacks, a 30-year-old Black woman, was treated for cervical cancer at Johns Hopkins Hospital in Baltimore. Cells from a biopsy of her tumor were given to researchers without her knowledge or consent; there were no federal rules then on using patients' cells in research. Her cells kept dividing in the laboratory, the first human cells to do so reliably. Henrietta Lacks died of her cancer that October, at 31, but the cell line, named HeLa after her, kept growing (see NIH 2013; Johns Hopkins Medicine; Lucey et al.). Within two years HeLa cells were being used to grow poliovirus for research (see Scherer et al.), and they are still used to study cancer, viruses and the cell cycle itself. In 2013 the NIH and the Lacks family reached an agreement on how researchers may use the genome data of HeLa cells (see NIH-Lacks Family Agreement).

Chromosomes were first seen as stained threads in dividing cells. It took nearly eighty years to connect those threads to heredity, to the halving in meiosis, to inherited disorders and to the proteins that run the cycle.