7. A Bit Like a Line Dance

Having been just reviewed the cell cycle we now focus on the fourth step of that process, mitosis, where the two genomes are pulled into their new cells. This is an amazing feat of cellular choreography that I liken to a line dance.

Let's take a quick look at the entire mitosis process from start to finish before covering each step in more detail. The entry point is the very end of interphase--that is, the combination of phases G1, S, and G2. The genome has been copied and all the chromosomes in the nucleus is in the form of long, stringy, tangled DNA.

In the first phase of mitosis, these condense into compact, visible structures (prophase). They then make their way to an imaginary line across the middle of the cell and molecular cables attach each to structures at the two poles of the cell (metaphase). The cables pull the chromosomes toward each pole (anaphase). There, the chromosomes de-condense and two new nuclear membranes form around them creating two new nuclei (telophase). Finally, the cell pinches in the middle and become two cells (cytokinesis).

Interphase: The Dancers Haven't Arrived Yet

Our starting point (not mitosis yet) is a cell that has passed through G2 after replicating its genome in S phase. A human genome has 23 chromosomes. We're born with genomes from both of our parents, so we have 46 chromosomes. But the G2 nucleus contains four full genomes, or 92 chromosomes all jumbled and intertwined. Think of 92 long strands of yarn stuffed into a small knitting bag.

The chromosomes can't be distinguished yet visually. But note an important detail in the figure below: two small star-like objects float outside the nucleus. These are centrosomes. They'll soon play a key role in chromosome movement.

Interphase Prophase Metaphase

Prophase: The Dancers Appear

At prophase, the stringy chromosomes are compacted and the centrosomes move to opposite poles. The long, intertwined chromosomes in the nucleus are untangled by specialized protein complexes, and then looped and coiled into compact units by other specialized protein complexes.

Hundreds to thousands of special ring-shaped proteins are loaded onto the chromosomes and encircle them, holding their arms (the "chromatids") together--much like rings around a pair of wires. The highest concentration of these proteins is at the centromeres. Now the chromosomes are in a form that can be pulled into the new daughter cells. These are our line dancers.

Let's pause to take a look at one of these condensed chromosomes and clarify terminology. When each chromosome was copied prior to mitosis, the original and the copy ended up attached at their middle regions, or centromeres, by those ring-shaped proteins. What biology textbooks refer to as "the chromosome" at this point looks like an "X" with the left side being referred to as one chromatid and the right side the other chromatid (sister chromatids).

Chromosomes and chromatids

I find this standard nomenclature confusing so let me try a different approach. The two left-hand arms of the "X" (called a "chromatid" in the figure) are actually one complete chromosome and the two right-hand arms are the other complete chromosome that was just synthesized. What I referred to in the last paragraph as "the chromosome" (the "X" shaped object) is really two identical chromosomes connected at their centers. So, bottom line: the 92 chromosomes actually take the form of 46 of these X-shaped bodies. Going forward I'll be downplaying the term "chromatid" even though it is used among scientists.

Back to prophase. In addition to condensing their chromosomes, cells begin reorganizing their internal scaffolding. The two centrosomes move to opposite ends of the cell while arrays of microtubules assemble between them. Together, these microtubules form the mitotic spindle—a dynamic, self-organizing structure that will soon capture and move chromosomes. By the end of prophase, the centrosomes are positioned at opposite poles, with spindle microtubules radiating outward and, in some cases, overlapping across the cell’s center.

Two final acts complete prophase. First, the nuclear membrane breaks down into fragments, which will later be recycled to form new nuclei in the daughter cells. This exposes the chromosomes to the mitotic spindle. Second, specialized protein hooks form at the chromosomes’ centromeres. These act as docking sites for spindle microtubules, allowing the mitotic spindle to attach to chromosomes and, in the next phase, begin pulling them apart.

Metaphase: The Dancers Line Up

The 46 X-shaped "double chromosomes" line up next to each other at the center, or equator, of the cell. The centrosomes--which are now at opposite ends of the cell--send out more mitotic spindles that attach to the molecular hooks. By the end of metaphase, all 46 chromosomes (92 chromatids) will be aligned along the equator and each of their hooks will be attached to a mitotic spindle emanating from one or the other of the centrosomes.

Anaphase: The Dance Begins

At the start of anaphase, the cell releases the bonds that have been holding each pair of chromosomes together. The enzyme responsible has been waiting in an inactive state as a safety precaution. Only when the cell confirms that every chromosome is properly aligned does the enzyme switch on. It then cuts the protein rings linking the chromosomes, allowing them to separate and be pulled apart.

The chromosomes are pulled toward the centrosomes by a process in which the mitotic spindle fibers shorten in a controlled way, pulling the chromosomes toward opposite ends of the cell. At the same time, other mitotic spindles that connect the two centrosomes do the opposite: they grow, lengthening out the cell in preparation for cell cleavage.

Anaphase Telophase Daughter cells

Telophase: Two New Dance Troupes Form

Two things happen in telophase. First, fragments of the nuclear membrane broken down at the end of prophase are recycled to create two new nuclear membranes around the chromosomes in the daughter cells. Second, the cell begins pinching inward at the equator. This begins the process of distributing cell parts (e.g., organelles, macromolecules, metabolites and ions) equally around the parent cell so that when the cell does pinch off (a process called cytokinesis) each will have what it needs to function. Finally, the compacted chromosomes de-compact in their new nuclei. This completes cell division.

Mitosis microscopy: High scale magnification of plant cells in metaphase (upper right) and in late anaphase (lower left)