Editing Mitosis (section)

==Phases==
{{Main|Cell cycle}}

===Overview===
[[File:Mitosis drosophila larva.ogv|thumb|150px|right|Time-lapse video of mitosis in a ''[[Drosophila melanogaster]]'' [[embryo]]]]
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 [[DNA sequence|genetic information]] vital for proper cell function.<ref>{{cite book |last1=Brown |first1=Terence A. |title=Genomes |date=2002 |publisher=Wiley-Liss |edition=2nd |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK21134/ |chapter=The Human Genome }}</ref> Because each resultant daughter cell should be [[clone (genetics)|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.<ref name="Blow-2005"/> [[DNA replication|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. [[Microtubule]]s 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.<ref name="Zhou-2002"/> 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 cell]]s, a [[cleavage furrow|cell membrane pinches inward]] between the two developing nuclei to produce two new cells. In [[plant cell]]s, a [[cell plate]] forms between the two nuclei. Cytokinesis does not always occur; coenocytic (a type of multinucleate condition) cells undergo mitosis without cytokinesis.

{{wide image|Mitosis Stages.svg|1100px|Diagram of [[interphase]] and the following five mitotic stages of the M phase including [[cytokinesis]].}}

===Interphase===
<!-- that graph and the following paragraph must have full labels not just single letters -->
{{main|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 phase|G<sub>1</sub> (first gap)]], [[S phase|S (synthesis)]], and [[G2 phase|G<sub>2</sub> (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 (G<sub>1</sub>), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G<sub>2</sub>), and finally divides (M) before restarting the cycle.<ref name="Blow-2005"/> 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 checkpoint]]s that give the cell cues to proceed or not, from one phase to another.<ref>{{cite web |last1=Biology Online |title= Mitosis |url=https://www.biologyonline.com/dictionary/mitosis |website=Biology Online|date= 28 April 2020 }}</ref> Cells may also temporarily or permanently leave the cell cycle and enter [[G0 phase|G<sub>0</sub> phase]] to stop dividing. This can occur when cells become overcrowded ([[density-dependent inhibition]]) or when they [[Cellular differentiation|differentiate]] to carry out specific functions for the organism, as is the case for [[Cardiac muscle cell|human heart muscle cells]] and [[neurons]]. Some G<sub>0</sub> cells have the ability to re-enter the cell cycle.

DNA double-strand breaks can be [[DNA repair|repaired]] during interphase by two principal processes.<ref>{{cite journal | pmid = 28781144 | doi=10.1016/j.mrfmmm.2017.07.011 | volume=803-805 | title=Regulation of repair pathway choice at two-ended DNA double-strand breaks | year=2017 | journal=Mutat Res | pages=51–55  | vauthors = Shibata A | bibcode=2017MRFMM.803...51S }}</ref>  The first process, [[non-homologous end joining]] (NHEJ), can join the two broken ends of DNA in the [[G1 phase|G1]], [[S phase|S]] and [[G2 phase|G2]] phases of interphase.  The second process, [[homologous recombination]]al 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 [[chromatids|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.<ref>{{cite journal |last1=Bernat |first1=R L |last2=Borisy |first2=G G |last3=Rothfield |first3=N F |last4=Earnshaw |first4=W C |title=Injection of anticentromere antibodies in interphase disrupts events required for chromosome movement at mitosis |journal=The Journal of Cell Biology |date=October 1990 |volume=111 |issue=4 |pages=1519–1533 |doi=10.1083/jcb.111.4.1519 |pmid=2211824 |pmc=2116233 }}</ref>

===Mitosis===
[[File:Stages of early mitosis in a vertebrate cell with micrographs of chromatids.svg|thumb|right|Stages of early mitosis in a vertebrate cell with [[micrograph]]s of [[chromatid]]s]]

====Preprophase (plant cells)====
{{main|Preprophase}}
In plant cells only, prophase is preceded by a [[preprophase]] stage. In highly [[vacuole|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 apparatus|spindle]]. This band marks the position where the cell will eventually divide. The cells of higher plants (such as the [[flowering plant]]s) 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.<ref name="Lloyd-2006"/> The preprophase band disappears during nuclear envelope breakdown and spindle formation in prometaphase.<ref name="Raven-2005">{{cite book | vauthors = Raven PH, Evert RF, Eichhorn SE |title= Biology of Plants |url= https://archive.org/details/biologyofplants00rave_0 |url-access= registration |edition= 7th |publisher= [[W. H. Freeman and Company|W. H. Freeman and Co.]] |year= 2005 |location= New York |isbn= 978-0716710073}}</ref>{{rp|58–67}}

====Prophase====
{{main|Prophase}}
[[File:CONDENSING CHROMOSOMES 2.jpg|thumb|left|Interphase nucleus (left), condensing chromosomes (middle) and condensed chromosomes (right)]]

[[File:Prophase diagram.svg|thumb|[[Prophase]] during mitosis]]

During prophase, which occurs after G<sub>2</sub> 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 G<sub>1</sub> phase.<ref>{{cite journal | vauthors = Prasanth KV, Sacco-Bubulya PA, Prasanth SG, Spector DL | title = Sequential entry of components of the gene expression machinery into daughter nuclei | journal = Molecular Biology of the Cell | volume = 14 | issue = 3 | pages = 1043–57 | date = March 2003 | pmid = 12631722 | pmc = 151578 | doi = 10.1091/mbc.E02-10-0669 }}</ref><ref>
{{cite journal | vauthors = Kadauke S, Blobel GA | title = Mitotic bookmarking by transcription factors | journal = Epigenetics & Chromatin | volume = 6 | issue = 1 | pages = 6 | date = April 2013 | pmid = 23547918 | pmc = 3621617 | doi = 10.1186/1756-8935-6-6 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Prescott DM, Bender MA | title = Synthesis of RNA and protein during mitosis in mammalian tissue culture cells | journal = Experimental Cell Research | volume = 26 | issue = 2 | pages = 260–8 | date = March 1962 | pmid = 14488623 | doi = 10.1016/0014-4827(62)90176-3 }}</ref> The [[nucleolus]] also disappears during early prophase.<ref>{{cite book | vauthors = Olson MO | date=2011 |title=The Nucleolus |volume=15 of Protein Reviews |location=Berlin |publisher=Springer Science & Business Media |page=15 |isbn=9781461405146 }}</ref>

Close to the nucleus of an animal cell are structures called [[centrosome]]s, consisting of a pair of [[centriole]]s surrounded by a [[Pericentriolar material|loose collection of proteins]]. The centrosome is the coordinating center for the cell's [[microtubule]]s. A cell inherits a single centrosome at cell division, which is [[Centrosome cycle|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 [[spindle apparatus|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,<ref name="Lloyd-2006"/> and are not absolutely required for animal cell mitosis.<ref name="Basto-2006">{{cite journal | vauthors = Basto R, Lau J, Vinogradova T, Gardiol A, Woods CG, Khodjakov A, Raff JW | title = Flies without centrioles | journal = Cell | volume = 125 | issue = 7 | pages = 1375–86 | date = June 2006 | pmid = 16814722 | doi = 10.1016/j.cell.2006.05.025 | doi-access = free }}</ref>

====Prometaphase====
{{main|Prometaphase}}
At the beginning of prometaphase in animal cells, phosphorylation of [[lamin|nuclear lamins]] causes the [[nuclear envelope]] to disintegrate into small membrane [[Vesicle (biology and chemistry)|vesicles]]. As this happens, microtubules invade the nuclear space. This is called ''open mitosis'', and it occurs in some multicellular organisms. Fungi and some [[protist]]s, such as [[algae]] or [[trichomonad]]s, undergo a variation called ''closed mitosis'' where the spindle forms inside the nucleus, or the microtubules penetrate the intact nuclear envelope.<ref name="Heywood-1978"/><ref name="Ribeiro-2002"/>

In late prometaphase, ''kinetochore microtubules'' begin to search for and attach to chromosomal [[kinetochores]].<ref name="Chan-2005"/> A ''kinetochore'' is a [[protein]]aceous microtubule-binding structure that forms on the chromosomal centromere during late prophase.<ref name="Chan-2005"/><ref>{{cite journal | vauthors = Cheeseman IM, Desai A | title = Molecular architecture of the kinetochore-microtubule interface | journal = Nature Reviews. Molecular Cell Biology | volume = 9 | issue = 1 | pages = 33–46 | date = January 2008 | pmid = 18097444 | doi = 10.1038/nrm2310 }}</ref> A number of ''polar microtubules'' find and interact with corresponding polar microtubules from the opposite centrosome to form the mitotic spindle.<ref name="Winey-1995"/> Although the kinetochore structure and function are not fully understood, it is known that it contains some form of [[List of gene families#Motor proteins|molecular motor]].<ref name="Maiato-2004"/> When a microtubule connects with the kinetochore, the motor activates, using energy from [[Adenosine triphosphate|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.<ref name="Maiato-2004"/>

====Metaphase====
[[File:Mitosis-fluorescent.jpg|thumb|right|A cell in late [[metaphase]]. All chromosomes (blue) but one have arrived at the [[metaphase plate]].]] 
{{main|Metaphase}}

[[File:Metaphase during Mitosis.svg|thumb|[[Metaphase]] during mitosis]]

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).<ref name="Winey-1995"/> To ensure equitable distribution of chromosomes at the end of mitosis, the ''[[spindle checkpoint|metaphase checkpoint]]'' guarantees that kinetochores are properly attached to the mitotic spindle and that the chromosomes are aligned along the metaphase plate.<ref name="Chan-2003"/> If the cell successfully passes through the metaphase checkpoint, it proceeds to anaphase.

====Anaphase====
{{main|Anaphase}}

[[File:Anaphase during Mitosis.svg|thumb|[[Anaphase]] during mitosis]]

During ''anaphase A'', the [[cohesin]]s that bind sister chromatids together are cleaved, forming two identical daughter chromosomes.<ref name="FitzHarris-2012"/> 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.<ref name="Miller-2000"/> In late anaphase, [[chromosome]]s also reach their overall maximal condensation level, to help [[chromosome segregation]] and the re-formation of the nucleus.<ref>{{cite press release |title=Researchers Shed Light On Shrinking Of Chromosomes |url=https://www.sciencedaily.com/releases/2007/06/070611122252.htm |work=ScienceDaily |publisher=European Molecular Biology Laboratory |date=12 June 2007 }}</ref> In most animal cells, anaphase A precedes anaphase B, but some vertebrate egg cells demonstrate the opposite order of events.<ref name="FitzHarris-2012">{{cite journal | vauthors = FitzHarris G | title = Anaphase B precedes anaphase A in the mouse egg | journal = Current Biology | volume = 22 | issue = 5 | pages = 437–44 | date = March 2012 | pmid = 22342753 | doi = 10.1016/j.cub.2012.01.041 | doi-access = free | bibcode = 2012CBio...22..437F }}</ref>

====Telophase====
{{main|Telophase}}

[[File:Telophase during Mitosis.svg|thumb|[[Telophase]] during mitosis]]

Telophase (from the [[Greek language|Greek]] word ''τελος'' meaning "end") is a reversal of prophase and prometaphase events. At telophase, the polar microtubules continue to lengthen, elongating the cell even more. If the nuclear envelope has broken down, a new nuclear envelope forms using the membrane vesicles of the parent cell's old nuclear envelope. The new envelope forms around each set of separated daughter chromosomes (though the membrane does not enclose the centrosomes) and the nucleolus reappears. Both sets of chromosomes, now surrounded by new nuclear membrane, begin to "relax" or decondense. Mitosis is complete. Each daughter nucleus has an identical set of chromosomes. Cell division may or may not occur at this time depending on the organism.

===Cytokinesis===
{{main|Cytokinesis}}

[[File:Cytokinesis illustration.svg|thumb|right|Cytokinesis illustration]]
[[File:Unk.cilliate.jpg|thumb|left|[[Ciliate]] undergoing [[cytokinesis]], with the [[cleavage furrow]] being clearly visible]]

[[Cytokinesis]] is not 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.<ref name="Glotzer-2005"/> 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.<ref name="Albertson-2005"/> 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.<ref name="Raven-2005"/>{{rp|64–7, 328–9}} 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.

There are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei. The most notable occurrence of this is among the [[fungus|fungi]], [[slime mold]]s, and coenocytic algae, but the phenomenon is found in various other organisms. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of [[Drosophila melanogaster|fruit fly]] embryonic development.<ref name="Lilly-2005"/>