Mitosis is the process by which a cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is a form of karyokinesis, or nuclear division. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles, and cell membrane into two cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle—the division of the mother cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 10% of the cell cycle. Mitosis occurs only in eukaryotic cells and the process varies in different species.
The mitotic phase is a relatively short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for cell division. Interphase is divided into three phases: G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and finally it divides (M) before restarting the cycle. All these phases in the cell cycle are highly regulated, mainly via proteins. The phases follow one another in strict order and there are “checkpoints” that give the cell the cues to proceed from one phase to another. There is also a fourth section in Interphase where the cell has the option to enter G0. Cells continue on through this cell cycle until they become too crowded; at that point they will exit the cell cycle and enter G0. This reaction is called contact inhibition or density-dependent inhibition. Altogether interphase takes up roughly 90% of a cell’s lifespan.
In plant cells only, prophase is preceded by a pre-prophase stage. In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell before mitosis can begin. This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm that bisects the cell along the future plane of cell division. In addition to phragmosome formation, preprophase is characterized by the formation of a ring of microtubules and actin filaments (called preprophase band) underneath the plasma membrane around the equatorial plane of the future mitotic spindle. This band marks the position where the cell will eventually divide. The cells of higher plants (such as the flowering plants) lack centrioles; instead, microtubules form a spindle on the surface of the nucleus and are then organized into a spindle by the chromosomes themselves, after the nuclear membrane dissolves. The preprophase band disappears during nuclear membrane dissolution and spindle formation in prometaphase.
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin fibers become tightly coiled, condensing into discrete chromosomes. It is crucial for the reader to note that chromatin is a complex consisting of both chromosomes and specific proteins. Since the genetic material has already been duplicated earlier in S phase, the replicated chromosomes have two sister chromatids, bound together at the centromere by the cohesin protein complex. Chromosomes are typically visible at high magnification through a light microscope.
Also inside the nucleus, the nucleolus in the nucleus disappears from view. This is noteworthy because the cell does not need to divide the nucleolus right away. It will later reform when the nucleus divides completely.
Close to the nucleus are structures called centrosomes, consisting of a pair of centrioles, and actin, a halo of microtubule fragments, centrioles are found in most eukaryotic animal cells. The centrosome is the coordinating center for the cell’s microtubules. A cell inherits a single centrosome at cell division, which is replicated by the cell with the help of the nucleus before a new mitosis begins, giving a pair of centrosomes. The two centrosomes nucleate microtubules (which may be thought of as cellular ropes or poles) to form the spindle by polymerizing soluble tubulin. Molecular motor proteins then push the centrosomes along these microtubules to opposite sides of the cell. Although centrioles help organize microtubule assembly, they are not essential for the formation of the spindle, since they are absent from plants, and centrosomes are not always used in mitosis.
Note: Prometaphase is sometimes included as part of the end of prophase and early metaphase.
During early prometaphase, the nuclear membrane disintegrates and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Fungi and some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the spindle forms inside the nucleus, or its microtubules are able to penetrate an intact nuclear membrane, which stays intact.
In late prometaphase, each chromosome forms two kinetochores at its centromere, one attached at each chromatid. A kinetochore is a complex protein structure that is analogous to a ring for the microtubule hook; it is the point where microtubules attach themselves to the chromosome. Although the kinetochore structure and function are not fully understood, it is known that it contains some form of molecular motor. When a microtubule connects with the kinetochore, the motor activates, using energy from ATP to “crawl” up the tube toward the originating centrosome. This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides the pulling force necessary to later separate the chromosome’s two chromatids.
When the spindle grows to sufficient length, kinetochore microtubules begin searching for kinetochores to attach to. A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle.
In the fishing pole analogy, the kinetochore would be the “hook” that catches a sister chromatid or “fish”. The centrosome acts as the “reel” that draws in the spindle fibers or “fishing line”. It is also one of the main phases of mitosis because without it cytokinesis would not be able to occur.
Metaphase came from the Greek μετα meaning “after.” After the microtubules have found and attached to the kinetochores in prometaphase, the two centrosomes start pulling the chromosomes through their attached centromeres towards the two ends of the cell. As a result, the chromosomes come under longitudinal tension from the two ends of the cell. The centromeres of the chromosomes, in some sense, convene along the metaphase plate or equatorial plane, an imaginary line that is right in between the two centrosome poles. This line is called the spindle equator. This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between people of equal strength. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only roughly lining up along the midline.
Because proper chromosome separation requires that every kinetochore be attached to a bundle of microtubules (spindle fibres), it is thought that unattached kinetochores generate a signal to prevent premature progression to anaphase without all chromosomes being aligned. The signal creates the mitotic spindle checkpoint.
When every kinetochore is attached to a cluster of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds to anaphase (from the Greek ανα meaning “up,” “against,” “back,” or “re-“).
Two events then occur: first, the proteins that bind sister chromatids together are cleaved. These sister chromatids now become separate daughter chromosomes, and are pulled apart by shortening kinetochore microtubules and move toward the respective centrosomes to which they are attached. The cleaved centromeres go first while the chromatids trail behind. They all look like they’re trying to grab at their partners, because they become shaped like a V.
Next, the polar microtubules elongate, pulling the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell. The force that causes the centrosomes to move towards the ends of the cell is still unknown, although there is a theory that suggests that the rapid assembly and breakdown of microtubules may cause this movement. At the end of anaphase the kinecticore microtubules all degrade.
Telophase (from the Greek τελος meaning “end”) is a reversal of prophase and prometaphase events. It “cleans up” the after effects of mitosis. At telophase, the polar microtubules continue to lengthen, elongating the cell even more. Corresponding daughter chromosomes attach at opposite ends of the cell. A new nuclear membrane, using the membrane vesicles of the parent cell’s old nuclear membrane, forms around each set of separated daughter chromosomes (though the membrane does not enclose the centrosomes) The nucleoli reappear, too. Both sets of chromosomes, now surrounded by new nuclei, begin to “relax” or decondense back into chromatin. Mitosis is complete, but cell division is not.
Cytokinesis is often mistakenly thought to be the final part of telophase; however, cytokinesis is a separate process that begins at the same time as telophase. Cytokinesis is technically not even a phase of mitosis, but rather a separate process, necessary for completing cell division. In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei. In both animal and plant cells, cell division is also driven by vesicles derived from the Golgi apparatus, which move along microtubules to the middle of the cell. In plants this structure coalesces into a cell plate at the center of the phragmoplast and develops into a cell wall, separating the two nuclei. The phragmoplast is a microtubule structure typical for higher plants, whereas some green algae use a phycoplast microtubule array during cytokinesis. Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.