Mitosis is the process in which a eukaryotic cell separates the chromosomes in its cell nucleus, into two identical sets in two daughter nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two daughter 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.
Interphase
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 therefore not part of mitosis. 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 divides (M).
Preprophase
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: with microtubules forming a spindle on the surface of the nucleus and then being organized into a spindle by the chromosomes themselves, after the nuclear membrane breaks down. The preprophase band disappears during nuclear envelope disassembly and spindle formation in prometaphase.
Prophase
Prophase: The two round objects above the nucleus are the centrosomes. The chromatin has condensed.
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin condenses together into a highly ordered structure called a chromosome. 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 cohesion complex. Chromosomes are visible at high magnification through a light microscope.
Close to the nucleus are structures called centrosomes, which are made of a pair of centriole. The centrosome is the coordinating center for the cell's microtubules. A cell inherits a single centrosome at cell division, which replicates 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 side of the cell. Although centrosomes 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 meiosis.
Prometaphase
Micrograph showing condensed chromosomes in blue and the mitotic spindle in green during prometaphase of mitosis
Prometaphase: The nuclear membrane has degraded, and microtubules have invaded the nuclear space. These microtubules can attach to kinetochores or they can interact with opposing microtubules.
The nuclear envelope disassembles 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 envelope.
Each chromosome forms two kinetochores at the 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. Prometaphase is sometimes considered part of prophase.
Metaphase
A cell in late metaphase. All chromosomes (blue) but one have arrived at the metaphase plate.
Metaphase: The chromosomes have aligned at the metaphase plate.
As microtubules find and attach to kinetochores in prometaphase, the centromeres of the chromosomes convene along the metaphase plate or equatorial plane, an imaginary line that is equidistant from the two centrosome poles. 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. Metaphase comes from the Greek μετα meaning "after."
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.
Anaphase
Early anaphase: Kinetochore microtubules shorten
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, allowing them to separate. These sister chromatids, which have now become distinct sister chromosomes, are pulled apart by shortening kinetochore microtubules and move toward the respective centrosomes to which they are attached. Next, the nonkinetochore microtubules elongate, pushing 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.
These two stages are sometimes called early and late anaphase. Early anaphase is usually defined as the separation of the sister chromatids, while late anaphase is the elongation of the microtubules and the microtubules being pulled farther apart. At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.
Telophase
Telophase: The decondensing chromosomes are surrounded by nuclear membranes. Note cytokinesis has already begun, the pinching is known as the cleavage furrow.
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 nonkinetochore microtubules continue to lengthen, elongating the cell even more. Corresponding sister chromosomes attach at opposite ends of the cell. A new nuclear envelope, using fragments of the parent cell's nuclear membrane, forms around each set of separated sister chromosomes. Both sets of chromosomes, now surrounded by new nuclei, unfold back into chromatin. Mitosis is complete, but cell division is not yet complete.
Cytokinesis
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.
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