Cell division

Cell division is the process by which a parent cell divides into two daughter cells.^[1] Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells.^[2] Mitosis is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis (division of the nucleus) is preceded by the S stage of interphase (during which the DNA replication occurs) and is followed by telophase and cytokinesis; which divides 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 all together define the M phase of an animal cell cycle—the division of the mother cell into two genetically identical daughter cells.^[3] To ensure proper progression through the cell cycle, DNA damage is detected and repaired at various checkpoints throughout the cycle. These checkpoints can halt progression through the cell cycle by inhibiting certain cyclin-CDK complexes. Meiosis undergoes two divisions resulting in four haploid daughter cells. Homologous chromosomes are separated in the first division of meiosis, such that each daughter cell has one copy of each chromosome. These chromosomes have already been replicated and have two sister chromatids which are then separated during the second division of meiosis.^[4] Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

Prokaryotes (bacteria and archaea) usually undergo a vegetative cell division known as binary fission, where their genetic material is segregated equally into two daughter cells, but there are alternative manners of division, such as budding, that have been observed. All cell divisions, regardless of organism, are preceded by a single round of DNA replication.

For simple unicellular microorganisms such as the amoeba, one cell division is equivalent to reproduction – an entire new organism is created. On a larger scale, mitotic cell division can create progeny from multicellular organisms, such as plants that grow from cuttings. Mitotic cell division enables sexually reproducing organisms to develop from the one-celled zygote, which itself is produced by fusion of two gametes, each having been produced by meiotic cell division.^[5][6] After growth from the zygote to the adult, cell division by mitosis allows for continual construction and repair of the organism.^[7] The human body experiences about 10 quadrillion cell divisions in a lifetime.^[8]

The primary concern of cell division is the maintenance of the original cell's genome. Before division can occur, the genomic information that is stored in chromosomes must be replicated, and the duplicated genome must be cleanly divided between progeny cells.^[9] A great deal of cellular infrastructure is involved in ensuring consistency of genomic information among generations.^[10][11][12]

Bacterial cell division happens through binary fission or through budding. The divisome is a protein complex in bacteria that is responsible for cell division, constriction of inner and outer membranes during division, and remodeling of the peptidoglycan cell wall at the division site. A tubulin-like protein, FtsZ plays a critical role in formation of a contractile ring for the cell division.^[14]

Cell division in eukaryotes is more complicated than in prokaryotes. If the chromosomal number is reduced, eukaryotic cell division is classified as meiosis (reductional division). If the chromosomal number is not reduced, eukaryotic cell division is classified as mitosis (equational division). A primitive form of cell division, called amitosis, also exists. The amitotic or mitotic cell divisions are more atypical and diverse among the various groups of organisms, such as protists (namely diatoms, dinoflagellates, etc.) and fungi.^{[citation needed]}

In the mitotic metaphase (see below), typically the chromosomes (each containing 2 sister chromatids that developed during replication in the S phase of interphase) align themselves on the metaphase plate. Then, the sister chromatids split and are distributed between two daughter cells.^{[citation needed]}

In meiosis I, the homologous chromosomes are paired before being separated and distributed between two daughter cells. On the other hand, meiosis II is similar to mitosis. The chromatids are separated and distributed in the same way. In humans, other higher animals, and many other organisms, the process of meiosis is called gametic meiosis, during which meiosis produces four gametes. Whereas, in several other groups of organisms, especially in plants (observable during meiosis in lower plants, but during the vestigial stage in higher plants), meiosis gives rise to spores that germinate into the haploid vegetative phase (gametophyte). This kind of meiosis is called sporic meiosis.^{[citation needed]}

Cells are broadly classified into two main categories: simple non-nucleated prokaryotic cells and complex nucleated eukaryotic cells. Due to their structural differences, eukaryotic and prokaryotic cells do not divide in the same way. Also, the pattern of cell division that transforms eukaryotic stem cells into gametes (sperm cells in males or egg cells in females), termed meiosis, is different from that of the division of somatic cells in the body.

In 2022, scientists discovered a new type of cell division called asynthetic fission found in the squamous epithelial cells in the epidermis of juvenile zebrafish. When juvenile zebrafish are growing, skin cells must quickly cover the rapidly increasing surface area of the zebrafish. These skin cells divide without duplicating their DNA (the S phase of mitosis) causing up to 50% of the cells to have a reduced genome size. These cells are later replaced by cells with a standard amount of DNA. Scientists expect to find this type of division in other vertebrates.^[39]

DNA damage is detected and repaired at various points in the cell cycle. The G1/S checkpoint, G2/M checkpoint, and the checkpoint between metaphase and anaphase all monitor for DNA damage and halt cell division by inhibiting different cyclin-CDK complexes. The p53 tumor-suppressor protein plays a crucial role at the G1/S checkpoint and the G2/M checkpoint. Activated p53 proteins result in the expression of many proteins that are important in cell cycle arrest, repair, and apoptosis. At the G1/S checkpoint, p53 acts to ensure that the cell is ready for DNA replication, while at the G2/M checkpoint p53 acts to ensure that the cells have properly duplicated their content before entering mitosis.^[40]

Specifically, when DNA damage is present, ATM and ATR kinases are activated, activating various checkpoint kinases.^[41] These checkpoint kinases phosphorylate p53, which stimulates the production of different enzymes associated with DNA repair.^[42] Activated p53 also upregulates p21, which inhibits various cyclin-cdk complexes. These cyclin-cdk complexes phosphorylate the Retinoblastoma (Rb) protein, a tumor suppressor bound with the E2F family of transcription factors. The binding of this Rb protein ensures that cells do not enter the S phase prematurely; however, if it is not able to be phosphorylated by these cyclin-cdk complexes, the protein will remain, and the cell will be halted in the G1 phase of the cell cycle.^[43]

If DNA is damaged, the cell can also alter the Akt pathway in which BAD is phosphorylated and dissociated from Bcl2, thus inhibiting apoptosis. If this pathway is altered by a loss of function mutation in Akt or Bcl2, then the cell with damaged DNA will be forced to undergo apoptosis.^[44] If the DNA damage cannot be repaired, activated p53 can induce cell death by apoptosis. It can do so by activating the p53 upregulated modulator of apoptosis (PUMA). PUMA is a pro-apoptotic protein that rapidly induces apoptosis by inhibiting the anti-apoptotic Bcl-2 family members.^[45]

Multicellular organisms replace worn-out cells through cell division. In some animals, however, cell division eventually halts. In humans this occurs, on average, after 52 divisions, known as the Hayflick limit. The cell is then referred to as senescent. With each division the cells telomeres, protective sequences of DNA on the end of a chromosome that prevent degradation of the chromosomal DNA, shorten. This shortening has been correlated to negative effects such as age-related diseases and shortened lifespans in humans.^[46][47] Cancer cells, on the other hand, are not thought to degrade in this way, if at all. An enzyme complex called telomerase, present in large quantities in cancerous cells, rebuilds the telomeres through synthesis of telomeric DNA repeats, allowing division to continue indefinitely.^[48]

At the beginning of the 19th century, various hypotheses circulated about cell proliferation, which became observable in plant and animal organisms as a result of advances in microscopy. While the proliferation of cells on the inner side of old cells,^[49][50] the attachment of vesicles to existing cells,^[51] or crystallization in the intercellular space^[52] were postulated as mechanisms of cell proliferation, cell division itself had to fight for its acceptance for decades.

The Belgian botanist Barthélemy Charles Joseph Dumortier must be regarded as the first discoverer of cell division. In 1832, he described cell division in simple aquatic plants (French 'conferve') as follows (translated from French to English):

"The development of the conferve is as simple as its structure; it takes place by the attachment of new cells to the old, and this attachment always takes place from the end. The terminal cell elongates more than the deeper cells; then the production of a lateral bisector takes place in the inner fluid, which tends to divide the cell into two parts, of which the deeper one remains stationary, while the terminal part elongates again, forms a new inner partition, and so on. Is the production of the middle partition originally double or single? It is impossible to determine this, but it is always true that it later appears double when united, and that when two cells naturally separate, each of them is closed at both ends."^[53]

In 1835, the German botanist and physician Hugo von Mohl described plant cell division in much greater detail in his dissertation on freshwater and seawater algae for his PhD thesis in medicine and surgery:^[54]

"Among the most obscure phenomena of plant life is the manner in which the newly developing cells are formed. [...] and so there is no lack of manifold descriptions and explanations of this process. [...] and that gaps that were found in the observations were filled in by overly bold conclusions and assumptions." (translated from German to English)

In 1838, the German physician and botanist Franz Julius Ferdinand Meyen confirmed the mechanism of cell division at the root tips of plants.^[55] The German-Polish physician Robert Remak suspected that he had already discovered animal cell division in the blood of chicken embryos in 1841,^[56] but it was not until 1852 that he was able to confirm animal cell division for the first time in bird embryos, frog larvae and mammals.^[57]

In 1943, cell division was filmed for the first time^[58] by Kurt Michel using a phase-contrast microscope.^[59]

• Cell fusion
  • gametic fusion
• Cell growth
• Cyclin-dependent kinase
• Labile cells, cells that constantly divide
• Mitotic catastrophe