Process in which chromosomes are replicated and separated into two new identical nuclei
Mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the total number of chromosomes is maintained. Mitosis is preceded by the S phase of interphase (during which DNA replication occurs) and is followed by telophase and cytokinesis, which divide the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic phase (M phase) of a cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.
The process of mitosis is divided into stages corresponding to the completion of one set of activities and the start of the next. These stages are preprophase (specific to plant cells), prophase, prometaphase, metaphase, anaphase, and telophase. During mitosis, the chromosomes, which have already duplicated during interphase, condense and attach to spindle fibers that pull one copy of each chromosome to opposite sides of the cell. The result is two genetically identical daughter nuclei. The rest of the cell may then continue to divide by cytokinesis to produce two daughter cells. The different phases of mitosis can be visualized in real time, using live cell imaging.
An error in mitosis can result in the production of three or more daughter cells instead of the normal two. This is called tripolar mitosis and multipolar mitosis, respectively. These errors can be the cause of non-viable embryos that fail to implant. Other errors during mitosis can induce mitotic catastrophe, apoptosis (programmed cell death) or cause mutations. Certain types of cancers can arise from such mutations.
Mitosis occurs only in eukaryotic cells and varies between organisms. For example, animal cells generally undergo an open mitosis, where the nuclear envelope breaks down before the chromosomes separate, whereas fungal cells generally undergo a closed mitosis, where chromosomes divide within an intact cell nucleus. Most animal cells undergo a shape change, known as mitotic cell rounding, to adopt a near spherical morphology at the start of mitosis. Most human cells are produced by mitotic cell division. Important exceptions include the gametes – sperm and egg cells – which are produced by meiosis. Prokaryotes, bacteria and archaea which lack a true nucleus, divide by a different process called binary fission.
Discovery.
Numerous descriptions of cell division were made during 18th and 19th centuries, with various degrees of accuracy. In 1835, the German botanist Hugo von Mohl, described cell division in the green algae "Cladophora glomerata", stating that multiplication of cells occurs through cell division. In 1838, Matthias Jakob Schleiden affirmed that "formation of new cells "in their interior" was a general rule for cell multiplication in plants", a view later rejected in favour of Mohl's model, due to contributions of Robert Remak and others.
In animal cells, cell division with mitosis was discovered in frog, rabbit, and cat cornea cells in 1873 and described for the first time by the Polish histologist Wacław Mayzel in 1875.
Bütschli, Schneider and Fol might have also claimed the discovery of the process presently known as "mitosis". In 1873, the German zoologist Otto Bütschli published data from observations on nematodes. A few years later, he discovered and described mitosis based on those observations.
The term "mitosis", coined by Walther Flemming in 1882, is derived from the Greek word μίτος ("mitos", "warp thread"). There are some alternative names for the process, e.g., "karyokinesis" (nuclear division), a term introduced by Schleicher in 1878, or "equational division", proposed by August Weismann in 1887. However, the term "mitosis" is also used in a broad sense by some authors to refer to karyokinesis and cytokinesis together. Presently, "equational division" is more commonly used to refer to meiosis II, the part of meiosis most like mitosis.
Phases.
Overview.
The primary result of mitosis and cytokinesis is the transfer of a parent cell's genome into two daughter cells. The genome is composed of a number of chromosomes—complexes of tightly coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during the S phase of interphase. Chromosome duplication results in two identical "sister chromatids" bound together by cohesin proteins at the "centromere".
When mitosis begins, the chromosomes condense and become visible. In some eukaryotes, for example animals, the nuclear envelope, which segregates the DNA from the cytoplasm, disintegrates into small vesicles. The nucleolus, which makes ribosomes in the cell, also disappears. Microtubules project from opposite ends of the cell, attach to the centromeres, and align the chromosomes centrally within the cell. The microtubules then contract to pull the sister chromatids of each chromosome apart. Sister chromatids at this point are called "daughter chromosomes". As the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends of the cell and condense maximally in late anaphase. A new nuclear envelope forms around each set of daughter chromosomes, which decondense to form interphase nuclei.
During mitotic progression, typically after the anaphase onset, the cell may undergo cytokinesis. In animal cells, a cell membrane pinches inward between the two developing nuclei to produce two new cells. In plant cells, a cell plate forms between the two nuclei. Cytokinesis does not always occur; coenocytic (a type of multinucleate condition) cells undergo mitosis without cytokinesis.
Interphase.
The interphase is a much longer phase of the cell cycle than the relatively short M phase. During interphase the cell prepares itself for the process of cell division. Interphase is divided into three subphases: G1 (first gap), S (synthesis), and G2 (second gap). During all three parts of interphase, 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 divides (M) before restarting the cycle. All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. The phases follow one another in strict order and there are cell cycle checkpoints that give the cell cues to proceed or not, from one phase to another. Cells may also temporarily or permanently leave the cell cycle and enter G0 phase to stop dividing. This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific functions for the organism, as is the case for human heart muscle cells and neurons. Some G0 cells have the ability to re-enter the cell cycle.
DNA double-strand breaks can be repaired during interphase by two principal processes. The first process, non-homologous end joining (NHEJ), can join the two broken ends of DNA in the G1, S and G2 phases of interphase. The second process, homologous recombinational repair (HRR), is more accurate than NHEJ in repairing double-strand breaks. HRR is active during the S and G2 phases of interphase when DNA replication is either partially accomplished or after it is completed, since HRR requires two adjacent homologs.
Interphase helps prepare the cell for mitotic division. It dictates whether the mitotic cell division will occur. It carefully stops the cell from proceeding whenever the cell's DNA is damaged or has not completed an important phase. The interphase is very important as it will determine if mitosis completes successfully. It will reduce the amount of damaged cells produced and the production of cancerous cells. A miscalculation by the key Interphase proteins could be crucial as the latter could potentially create cancerous cells.
Mitosis.
Preprophase (plant cells).
In plant cells only, prophase is preceded by a preprophase 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 envelope breaks down. The preprophase band disappears during nuclear envelope breakdown and spindle formation in prometaphase.
Prophase.
During prophase, which occurs after G2 interphase, the cell prepares to divide by tightly condensing its chromosomes and initiating mitotic spindle formation. During interphase, the genetic material in the nucleus consists of loosely packed chromatin. At the onset of prophase, chromatin fibers condense into discrete chromosomes that are typically visible at high magnification through a light microscope. In this stage, chromosomes are long, thin, and thread-like. Each chromosome has two chromatids. The two chromatids are joined at the centromere.
Gene transcription ceases during prophase and does not resume until late anaphase to early G1 phase. The nucleolus also disappears during early prophase.
Close to the nucleus of an animal cell are structures called centrosomes, consisting of a pair of centrioles surrounded by a loose collection of proteins. The centrosome is the coordinating center for the cell's microtubules. A cell inherits a single centrosome at cell division, which is duplicated by the cell before a new round of mitosis begins, giving a pair of centrosomes. The two centrosomes polymerize tubulin to help form a microtubule spindle apparatus. Motor proteins then push the centrosomes along these microtubules to opposite sides of the cell. Although centrosomes help organize microtubule assembly, they are not essential for the formation of the spindle apparatus, since they are absent from plants, and are not absolutely required for animal cell mitosis.
Prometaphase.
At the beginning of prometaphase in animal cells, phosphorylation of nuclear lamins causes the nuclear envelope to disintegrate into small membrane vesicles. As this happens, microtubules invade the nuclear space. This is called "open mitosis", and it occurs in some 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 the microtubules penetrate the intact nuclear envelope.
In late prometaphase, "kinetochore microtubules" begin to search for and attach to chromosomal kinetochores. A "kinetochore" is a proteinaceous microtubule-binding structure that forms on the chromosomal centromere during late prophase. A number of "polar microtubules" find and interact with corresponding polar microtubules from the opposite centrosome to form the mitotic spindle. 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.
Metaphase.
After the microtubules have located and attached to the kinetochores in prometaphase, the two centrosomes begin pulling the chromosomes towards opposite ends of the cell. The resulting tension causes the chromosomes to align along the metaphase plate at the equatorial plane, an imaginary line that is centrally located between the two centrosomes (at approximately the midline of the cell). To ensure equitable distribution of chromosomes at the end of mitosis, the "metaphase checkpoint" guarantees that kinetochores are properly attached to the mitotic spindle and that the chromosomes are aligned along the metaphase plate. If the cell successfully passes through the metaphase checkpoint, it proceeds to anaphase.
Anaphase.
During "anaphase A", the cohesins that bind sister chromatids together are cleaved, forming two identical daughter chromosomes. Shortening of the kinetochore microtubules pulls the newly formed daughter chromosomes to opposite ends of the cell. During "anaphase B", polar microtubules push against each other, causing the cell to elongate. In late anaphase, chromosomes also reach their overall maximal condensation level, to help chromosome segregation and the re-formation of the nucleus. In most animal cells, anaphase A precedes anaphase B, but some vertebrate egg cells demonstrate the opposite order of events.
Telophase.
Telophase (from the Greek word "τελος" meaning "end") is a reversal of prophase and prometaphase