Editing Cell division (section)

== Phases of eukaryotic cell division ==

[[File:Animal cell cycle-en.svg|thumb|The phases (ordered counter-clockwise) of cell division ([[mitosis]]) and the [[cell cycle]] in animal cells.]]

=== Interphase ===
[[Interphase]] is the process through which a cell must go before mitosis, meiosis, and [[cytokinesis]].<ref>{{Cite book|title=Essentials of human anatomy and physiology| last = Marieb | first = Elaine Nicpon | name-list-style = vanc |date=2000 |publisher=Benjamin Cummings|isbn=978-0805349405|edition=6th|location=San Francisco|oclc=41266267}}</ref> Interphase consists of three main phases: [[G1 phase|G<sub>1</sub>]], [[S phase|S]], and [[G2 phase|G<sub>2</sub>]]. G<sub>1</sub> is a time of growth for the cell where specialized cellular functions occur in order to prepare the cell for DNA replication.<ref>{{cite journal | vauthors = Pardee AB | title = G1 events and regulation of cell proliferation | journal = Science | volume = 246 | issue = 4930 | pages = 603–8 | date = November 1989 | pmid = 2683075 | doi = 10.1126/science.2683075 | bibcode = 1989Sci...246..603P }}</ref> There are checkpoints during interphase that allow the cell to either advance or halt further development. One of the checkpoint is between G<sub>1</sub> and S, the purpose for this checkpoint is to check for appropriate cell size and any [[DNA damage]] . The second check point is in the G<sub>2</sub> phase, this checkpoint also checks for cell size but also the DNA replication. The last check point is located at the site of metaphase, where it checks that the chromosomes are correctly connected to the mitotic spindles.<ref>{{cite journal | vauthors = Molinari M | title = Cell cycle checkpoints and their inactivation in human cancer | journal = Cell Proliferation | volume = 33 | issue = 5 | pages = 261–74 | date = October 2000 | pmid = 11063129 | pmc = 6496592 | doi = 10.1046/j.1365-2184.2000.00191.x | url = }}</ref> In S phase, the chromosomes are replicated in order for the genetic content to be maintained.<ref>{{Cite book|title=The cell cycle : principles of control|last=Morgan | first = David Owen | name-list-style = vanc |date=2007|publisher=New Science Press|isbn=9780199206100|location=London|oclc=70173205}}</ref> During G<sub>2</sub>, the cell undergoes the final stages of growth before it enters the M phase, where [[Spindle apparatus|spindles]] are synthesized. The M phase can be either mitosis or meiosis depending on the type of cell. [[Germ cell]]s, or gametes, undergo meiosis, while [[somatic cell]]s will undergo mitosis. After the cell proceeds successfully through the M phase, it may then undergo cell division through cytokinesis. The control of each checkpoint is controlled by [[cyclin]] and [[cyclin-dependent kinase]]s. The progression of interphase is the result of the increased amount of cyclin. As the amount of cyclin increases, more and more cyclin dependent kinases attach to cyclin signaling the cell further into interphase. At the peak of the cyclin, attached to the cyclin dependent kinases this system pushes the cell out of interphase and into the M phase, where mitosis, meiosis, and cytokinesis occur.<ref>{{cite journal | vauthors = Lindqvist A, van Zon W, Karlsson Rosenthal C, Wolthuis RM | title = Cyclin B1-Cdk1 activation continues after centrosome separation to control mitotic progression | journal = PLOS Biology | volume = 5 | issue = 5 | pages = e123 | date = May 2007 | pmid = 17472438 | pmc = 1858714 | doi = 10.1371/journal.pbio.0050123 | doi-access = free }}</ref> There are three transition checkpoints the cell has to go through before entering the M phase. The most important being the G<sub>1</sub>-S transition checkpoint. If the cell does not pass this checkpoint, it results in the cell exiting the cell cycle.<ref>{{cite journal | vauthors = Paulovich AG, Toczyski DP, Hartwell LH | title = When checkpoints fail | journal = Cell | volume = 88 | issue = 3 | pages = 315–21 | date = February 1997 | pmid = 9039258 | doi = 10.1016/S0092-8674(00)81870-X | s2cid = 5530166 | doi-access = free }}</ref>

=== Prophase ===
[[Prophase]] is the first stage of division. The nuclear envelope begins to be broken down in this stage, long strands of chromatin condense to form shorter more visible strands called chromosomes, the nucleolus disappears, and the mitotic spindle begins to assemble from the two centrosomes.<ref>{{cite journal | vauthors = Schermelleh L, Carlton PM, Haase S, Shao L, Winoto L, Kner P, Burke B, Cardoso MC, Agard DA, Gustafsson MG, Leonhardt H, Sedat JW | display-authors = 6 | title = Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy | journal = Science | volume = 320 | issue = 5881 | pages = 1332–6 | date = June 2008 | pmid = 18535242 | pmc = 2916659 | doi = 10.1126/science.1156947 | bibcode = 2008Sci...320.1332S }}</ref> Microtubules associated with the alignment and separation of chromosomes are referred to as the spindle and spindle fibers. [[Chromosomes]] will also be visible under a microscope and will be connected at the centromere. During this condensation and alignment period in meiosis, the homologous chromosomes undergo a break in their double-stranded DNA at the same locations, followed by a recombination of the now fragmented parental DNA strands into non-parental combinations, known as crossing over.<ref>{{Cite journal|last1=Lewontin|first1=Richard C.|last2=Miller|first2=Jeffrey H.|last3=Gelbart|first3=William M.|last4=Griffiths|first4=Anthony J.F. | name-list-style = vanc |date=1999|title=The Mechanism of Crossing-Over|url=https://www.ncbi.nlm.nih.gov/books/NBK21271/ |journal=Modern Genetic Analysis }}</ref> This process is evidenced to be caused in a large part by the highly conserved [[Spo11]] protein through a mechanism similar to that seen with [[topoisomerase]] in DNA replication and transcription.<ref>{{cite book|last=Keeney|first=Scott|name-list-style=vanc|title=Mechanism and control of meiotic recombination initiation|volume=52|date=2001|pages=[https://archive.org/details/currenttopicsind0000scha_v7u9/page/1 1–53]|publisher=Elsevier|isbn=9780121531522|doi=10.1016/s0070-2153(01)52008-6|pmid=11529427|series=Current Topics in Developmental Biology|url=https://archive.org/details/currenttopicsind0000scha_v7u9/page/1}}</ref>

=== Prometaphase ===
[[Prometaphase]] is the second stage of cell division. This stage begins with the complete breakdown of the nuclear envelope which exposes various structures to the cytoplasm. This breakdown then allows the [[spindle apparatus]] growing from the [[centrosome]] to attach to the [[kinetochore]]s on the sister chromatids. Stable attachment of the spindle apparatus to the kinetochores on the sister chromatids will ensure error-free chromosome segregation during anaphase.<ref>{{cite book |doi=10.1016/B978-0-12-821618-7.30064-5 |chapter=Mitosis in Animal Cells |title=Encyclopedia of Cell Biology |date=2016 |last1=Lian |first1=A.T.Y. |last2=Chircop |first2=M. |pages=298–313 |isbn=978-0-12-821624-8 }}</ref> Prometaphase follows prophase and precedes metaphase.

=== Metaphase ===
In [[metaphase]], the [[centromere]]s of the chromosomes align themselves on the ''metaphase plate'' (or ''equatorial plate''), an imaginary line that is at equal distances from the two [[centrosome]] poles and held together by complexes known as [[cohesin]]s. Chromosomes line up in the middle of the cell by [[microtubule organizing center]]s (MTOCs) pushing and pulling on centromeres of both chromatids thereby causing the chromosome to move to the center. At this point the chromosomes are still condensing and are currently one step away from being the most coiled and condensed they will be, and the spindle fibers have already connected to the kinetochores.<ref>{{Cite web|url=https://www.sciencedaily.com/releases/2007/06/070611122252.htm|title=Researchers Shed Light On Shrinking Of Chromosomes|website=ScienceDaily | access-date=2019-04-14}}</ref> During this phase all the microtubules, with the exception of the kinetochores, are in a state of instability promoting their progression toward anaphase.<ref name=":3">{{Cite book |last1=Walter |first1=Peter |last2=Roberts |first2=Keith |last3=Raff |first3=Martin|last4=Lewis|first4=Julian|last5=Johnson|first5=Alexander|last6=Alberts|first6=Bruce | name-list-style = vanc |date=2002|chapter=Mitosis|url=https://www.ncbi.nlm.nih.gov/books/NBK26934/|title=Molecular Biology of the Cell|publisher=Garland Science | edition = 4th}}</ref> At this point, the chromosomes are ready to split into opposite poles of the cell toward the spindle to which they are connected.<ref>{{Cite book|title=Schaum's outlines : genetics|last=Elrod | first = Susan | name-list-style = vanc |date=2010 |publisher=Mcgraw-Hill |isbn=9780071625036 |edition=5th |location=New York |pages=8 |oclc=473440643}}</ref>

=== Anaphase ===
[[Anaphase]] is a very short stage of the cell cycle and it occurs after the chromosomes align at the mitotic plate. Kinetochores emit anaphase-inhibition signals until their attachment to the mitotic spindle. Once the final chromosome is properly aligned and attached the final signal dissipates and triggers the abrupt shift to anaphase.<ref name=":3" /> This abrupt shift is caused by the activation of the [[anaphase-promoting complex]] and its function of tagging degradation of proteins important toward the metaphase-anaphase transition. One of these proteins that is broken down is [[securin]] which through its breakdown releases the enzyme [[separase]] that cleaves the cohesin rings holding together the sister chromatids thereby leading to the chromosomes separating.<ref>{{cite book | vauthors = Brooker AS, Berkowitz KM | title = Cell Cycle Control | chapter = The Roles of Cohesins in Mitosis, Meiosis, and Human Health and Disease | series = Methods in Molecular Biology | volume = 1170 | pages = 229–66 | date = 2014 | pmid = 24906316 | pmc = 4495907 | doi = 10.1007/978-1-4939-0888-2_11 | publisher = Springer | location = New York | isbn = 9781493908875 }}</ref> After the chromosomes line up in the middle of the cell, the spindle fibers will pull them apart. The chromosomes are split apart while the sister chromatids move to opposite sides of the cell.<ref>{{Cite web|url=http://www.biology-pages.info/C/CellCycle.html|title=The Cell Cycle|website=www.biology-pages.info|access-date=2019-04-14}}</ref> As the sister chromatids are being pulled apart, the cell and plasma are elongated by non-kinetochore microtubules.<ref>{{cite book |title=Campbell Biology in Focus | location = Boston (Massachusetts) | publisher = Pearson | isbn = 978-0-321-81380-0 | date = 2014 | vauthors = Urry LA, Cain ML, Jackson RB, Wasserman SA, Minorsky PV, Reece JB }}</ref> Additionally, in this phase, the activation of the anaphase promoting complex through the association with [[CDH1 (gene)|Cdh-1]] begins the degradation of mitotic cyclins.<ref>{{Cite journal |last=Barford |first=David |date=2011-12-12 |title=Structural insights into anaphase-promoting complex function and mechanism |journal=Philosophical Transactions of the Royal Society B: Biological Sciences |language=en |volume=366 |issue=1584 |pages=3605–3624 |doi=10.1098/rstb.2011.0069 |pmid=22084387|pmc=3203452 }}</ref>

=== Telophase ===
[[Telophase]] is the last stage of the cell cycle in which a cleavage furrow splits the cells cytoplasm (cytokinesis) and chromatin. This occurs through the synthesis of a new nuclear envelope that forms around the chromatin gathered at each pole. The nucleolus reforms as the chromatin reverts back to the loose state it possessed during interphase.<ref>{{cite journal | vauthors = Dekker J | title = Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture | journal = Epigenetics & Chromatin | volume = 7 | issue = 1 | pages = 25 | date = 2014-11-25 | pmid = 25435919 | pmc = 4247682 | doi = 10.1186/1756-8935-7-25 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hetzer MW | title = The nuclear envelope | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 3 | pages = a000539 | date = March 2010 | pmid = 20300205 | pmc = 2829960 | doi = 10.1101/cshperspect.a000539 }}</ref> The division of the cellular contents is not always equal and can vary by cell type as seen with oocyte formation where one of the four daughter cells possess the majority of the duckling.<ref name=":22">{{Cite book|last=Gilbert|first=Scott F.| name-list-style = vanc |date=2000|chapter=Oogenesis|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK10008/ |title=Developmental Biology |publisher=Sinauer Associates | edition = 6th  }}</ref>

=== Cytokinesis ===
The last stage of the cell division process is [[cytokinesis]]. In this stage there is a cytoplasmic division that occurs at the end of either mitosis or meiosis. At this stage there is a resulting irreversible separation leading to two daughter cells. Cell division plays an important role in determining the fate of the cell. This is due to there being the possibility of an asymmetric division. This as a result leads to cytokinesis producing unequal daughter cells containing completely different amounts or concentrations of fate-determining molecules.<ref>{{cite journal | vauthors = Guertin DA, Trautmann S, McCollum D | title = Cytokinesis in eukaryotes | journal = Microbiology and Molecular Biology Reviews | volume = 66 | issue = 2 | pages = 155–78 | date = June 2002 | pmid = 12040122 | pmc = 120788 | doi = 10.1128/MMBR.66.2.155-178.2002 }}</ref>

In animals the cytokinesis ends with formation of a contractile ring and thereafter a cleavage. But in plants it happen differently. At first a cell plate is formed and then a cell wall develops between the two daughter cells.<ref>{{Cite journal |last=Smith |first=Laurie G |date=December 1999 |title=Divide and conquer: cytokinesis in plant cells |url=https://linkinghub.elsevier.com/retrieve/pii/S1369526699000229 |journal=Current Opinion in Plant Biology |language=en |volume=2 |issue=6 |pages=447–453 |doi=10.1016/S1369-5266(99)00022-9|pmid=10607656 |bibcode=1999COPB....2..447S |url-access=subscription }}</ref>

In Fission yeast ([[Schizosaccharomyces pombe|''S. pombe'']]) the cytokinesis happens in G1 phase.<ref>The Cell, G.M. Cooper; ed 2 [https://www.ncbi.nlm.nih.gov/books/NBK9876/ NCBI bookshelf], The eukaryotic cell cycle, [https://www.ncbi.nlm.nih.gov/books/NBK9876/ Figure 14.7]</ref>