Mitosis and the Cell Cycle

Every cell in your body came from another cell that divided. When a cell with a nucleus divides, it follows one big idea: copy the DNA first, then share the copies so that each new cell gets a complete set. This lesson follows that idea through the cell cycle, the four stages of mitosis, the splitting of the cytoplasm, and the counting of chromosomes. It also points out where the textbook model is simplified, so you know how far to trust it.

Why cells divide

Cells divide for three main reasons.

• Growth. A multicellular organism grows mostly by making more cells, not just by making each cell bigger. Cell size is limited: a cell that gets too big has too little membrane surface for its volume.
• Repair and replacement. Cells get damaged or wear out and have to be replaced. In your skin, cells in a deeper layer divide to replace the outer cells that wear away, and cells near a small cut divide to help fill in the gap.
• Asexual reproduction. Some organisms make new individuals by mitosis. A single-celled eukaryote such as an amoeba divides in two, and a strawberry plant sends out runners that grow into new plants. The offspring have the same DNA as the parent, apart from rare copying mistakes.

Mitosis happens in eukaryotic cells (cells with a nucleus). Bacteria are prokaryotes and have no nucleus, so they divide by a simpler process called binary fission, not by mitosis.

The cell cycle: interphase and M phase

The cell cycle is the series of events a cell goes through from one division to the next. It has two big parts:

1. Interphase is the stretch between divisions. It has three parts, always in this order: G1 (first gap), S (synthesis) and G2 (second gap).
2. M phase is the division itself. It has two processes: mitosis (division of the nucleus) and cytokinesis (division of the rest of the cell).

What happens in interphase:

• G1: the cell grows, makes proteins and new organelles, and does its normal job. Each chromosome is a single copy of its DNA.
• S: the cell copies (replicates) all of its DNA. When S ends, every chromosome consists of two identical copies, called sister chromatids, joined together. The number of chromosomes does not change.
• G2: the cell keeps growing and makes the proteins and other materials it needs in order to divide.

The G stands for gap: a gap between mitosis and DNA copying (G1) and a gap between DNA copying and mitosis (G2). The cell is not resting in these gaps. It is growing and working. During interphase the DNA is in a loosely packed form called chromatin, so you cannot see separate chromosomes as rods under a light microscope.

In a typical dividing cell, interphase takes up much more of the cycle than M phase does. Mitosis is not the whole cell cycle. Exact times vary a lot from one kind of cell to another.

Chromosomes, chromatids, centromeres and the spindle

A few words need exact meanings, because the counting rules depend on them.

• Chromosome: a long DNA molecule wrapped around proteins, carrying many genes. After S phase it has two identical DNA molecules, one in each sister chromatid, and it is still one chromosome. A typical human body cell has 46 chromosomes.
• Chromatin: the DNA-and-protein material of chromosomes. In interphase it is loose and spread out. In mitosis it coils up tightly into chromosomes that can be seen.
• Sister chromatids: the two identical copies of a chromosome made in S phase. They stay joined until anaphase. While they are joined, the pair is still one chromosome.
• Centromere: the region where the two sister chromatids are joined. Spindle fibers attach to the chromosome at the centromere. You count chromosomes by counting centromeres.
• Spindle: a structure of protein fibers (microtubules) that forms during mitosis and moves the chromosomes. In animal cells the spindle fibers grow from two centrosomes that move to opposite ends of the cell, called the poles. Flowering plant cells build a spindle too, but without centrosomes like those of animal cells.

An X-shaped chromosome in a diagram is a replicated chromosome: two sister chromatids joined at the centromere. Before S phase, and after anaphase, a chromosome has only one copy of its DNA and is drawn as a single rod. The X is a drawing convention. Real chromosomes are not always X-shaped, and the centromere is not always in the middle.

The four stages of mitosis (PMAT)

Mitosis is one smooth process, but textbooks split it into four stages so that we can name what is happening. A mnemonic for the order is PMAT: Prophase, Metaphase, Anaphase, Telophase. Interphase comes before PMAT and is not part of mitosis.

• Prophase. The chromatin coils up tightly, so each chromosome now shows up as two sister chromatids joined at a centromere. The nucleolus fades. The spindle starts to form as the two centrosomes move apart (in animal cells). Late in prophase the nuclear envelope breaks into pieces, and spindle fibers attach to the centromeres. (Some books call this late part prometaphase.)
• Metaphase. The chromosomes line up along the middle of the cell, in a flat plane called the metaphase plate. The plate is an imaginary plane, not a wall or any other structure. The two sister chromatids of each chromosome are attached to spindle fibers from opposite poles.
• Anaphase. The centromeres split, and the sister chromatids separate. From this moment each chromatid is called a chromosome. The spindle fibers shorten and pull the chromosomes toward opposite poles, while the cell stretches longer. Anaphase ends with a complete set of chromosomes at each pole.
• Telophase. The chromosomes reach the poles and begin to uncoil back into chromatin. A new nuclear envelope forms around each set, the nucleolus reappears, and the spindle breaks down. The cell now has two nuclei. Telophase is roughly prophase run in reverse.

The stages blend into each other, and where one stops and the next begins is a choice people made so they could talk about it. A cell caught between two stages is normal.

Cytokinesis: splitting the cell

Mitosis divides the nucleus. Cytokinesis divides the cytoplasm (the rest of the cell) so that the two new nuclei end up in two separate cells. It usually begins in late anaphase or telophase, so it overlaps the end of mitosis.

• Animal cells: a ring of protein fibers under the cell membrane tightens around the middle of the cell, like pulling a drawstring. The membrane pinches inward, forming a cleavage furrow, until the cell is pinched in two.
• Plant cells: a plant cell has a stiff cell wall, so it cannot simply pinch in two. Instead, small membrane bubbles (vesicles) carrying cell wall material gather in the middle of the cell and fuse to form a cell plate. The plate grows outward until it reaches the existing walls, and it becomes the new wall between the two daughter cells.

Be honest about the naming. In the strict textbook model, cytokinesis is not a stage of mitosis. Mitosis means division of the nucleus and ends with telophase. Cytokinesis is a separate process that overlaps with late mitosis. Some books list it as a fifth step, and others count it with mitosis as part of M phase. This lesson uses mitosis for PMAT and M phase for mitosis plus cytokinesis. The two processes can even be pulled apart: in some kinds of cells the nucleus divides but the cytoplasm does not, leaving one cell with two nuclei.

The result: two identical daughter cells

When mitosis and cytokinesis are finished, one parent cell has become two daughter cells. Each daughter cell has the same chromosome number as the parent and one copy of each of the parent's chromosomes. This works because S phase copied each chromosome and anaphase sent one sister chromatid of each chromosome to each pole. So the two daughter cells are genetically identical to each other and to the parent cell. (Rare copying mistakes, called mutations, can happen.)

Two limits are worth knowing:

• "Genetically identical" means the same DNA. The cells can still differ in other ways. Cytokinesis shares out the cytoplasm and organelles, and the two cells may not be exactly the same size.
• In a multicellular organism, cells with the same DNA can become different types of cells, such as skin cells and muscle cells, because different genes are switched on in them. This is called differentiation. Mitosis makes more cells, and differentiation gives them their jobs. Together they build and maintain a complex organism.

Counting chromosomes and chromatids

Use a human body cell as the model. A typical human body cell with a nucleus has 46 chromosomes in G1. Two rules keep the counting straight:

1. Count chromosomes by counting centromeres.
2. Sister chromatids are made during S phase and stay joined until anaphase. By the end of S phase every chromosome has two. While two sister chromatids are joined, together they count as one chromosome. Once they separate, each one is a chromosome, and you stop calling it a chromatid.

Now walk through the cycle:

• G1: 46 chromosomes. Each one is a single copy of its DNA, so there are no sister chromatids.
• End of S phase, G2, prophase and metaphase: still 46 chromosomes, because there are still 46 centromeres. Each chromosome now has two sister chromatids, so there are 92 chromatids.
• Anaphase and telophase, until cytokinesis is complete: the centromeres have split, so there are 92 chromosomes in the cell, 46 at each pole. There are no pairs of sister chromatids now.
• Once cytokinesis is complete: each daughter cell has 46 chromosomes.

The number 92 shows up twice: as 92 chromatids (in 46 chromosomes) from S phase to metaphase, and as 92 chromosomes (in one cell) from the start of anaphase until cytokinesis is complete. Copying the DNA doubles the amount of DNA and creates the pairs of sister chromatids, but it does not change the number of chromosomes. The number of chromosomes in the cell doubles at anaphase, and then each daughter cell gets back down to 46.

The limit: 46 is for a typical human body cell with a nucleus. Human egg and sperm cells have 23, mature red blood cells have no nucleus, and a few kinds of cells, such as some liver cells, have extra sets. Other species have other numbers, but the counting rules are the same.

Mitosis, meiosis and cancer

Mitosis is not the only way a cell divides. Meiosis is a different kind of division that cuts the chromosome number in half. In humans it makes sperm and egg cells with 23 chromosomes. It has its own lesson.

The cell cycle is controlled. At checkpoints, cells use chemical signals to decide whether to go on to the next stage. Cancer is a group of diseases in which cells divide without the normal controls that tell them when to stop. Scientists study these controls to understand what changes when they stop working. This lesson only explains the idea. It is not health advice.

Where this model stops

• The four stages are a naming tool. Mitosis is continuous, and some books add a fifth stage, prometaphase, between prophase and metaphase.
• Details differ among organisms. For example, in some fungi, such as yeasts, the nuclear envelope stays in place during mitosis.
• Not every cell keeps dividing. Some mature cells, such as most nerve cells in the brain, rarely or never divide again.
• The diagrams use 4 chromosomes to keep the pictures simple. A human body cell has 46.
• Cell cycle times are not fixed. They depend on the kind of cell and on conditions in the body.