Editing Cell cycle (section)

== Phases ==

The eukaryotic cell cycle consists of four distinct phases: [[G1 phase|G<sub>1</sub> phase]], [[S phase]] (synthesis), [[G2 phase|G<sub>2</sub> phase]] (collectively known as [[interphase]]) and [[Mitosis|M phase]] (mitosis and cytokinesis). M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's nucleus divides, and [[cytokinesis]], in which the cell's [[cytoplasm]] and cell membrane divides forming two daughter cells. Activation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence known as [[G0 phase|G<sub>0</sub> phase]] or ''resting phase''.
[[Image:Cell Cycle 2-2.svg|thumb|300px|Schematic of the cell cycle. Outer ring: I = [[Interphase]], M = [[Mitosis]]; inner ring: M = [[Mitosis]], G<sub>1</sub> = [[G1 phase|Gap 1]], G<sub>2</sub> = [[G2 phase|Gap 2]], S = [[S phase|Synthesis]]; not in ring: G<sub>0</sub> = [[G0 phase|Gap 0/Resting]]<ref name="isbn0-87893-106-6">{{cite book | vauthors = Cooper GM | title = The cell: a molecular approach | edition = 2nd | publisher = ASM Press | location = Washington, D.C. | year = 2000 | isbn = 978-0-87893-106-4 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK9876/ | chapter = Chapter 14: The Eukaryotic Cell Cycle | url-access = registration | url = https://archive.org/details/cell00geof }}</ref>]]
{| class="wikitable"  style="text-align:center"
|-
! State
! Phase
! Abbreviation
! Description
|-
|  Resting
| style="height:50px" | [[G0 phase|Gap 0]]
| '''G<sub>0</sub>'''
| align="left" width="500pt" | A phase where the cell has left the cycle and has stopped dividing.
|-
| rowspan="3" | [[Interphase]]
| style="height:50px" | [[G1 phase|Gap 1]]
| '''G<sub>1</sub>'''
| align="left" width="500pt" | Cell growth. The ''[[Cell cycle checkpoint#G1 .28Restriction.29 Checkpoint|G<sub>1</sub> checkpoint]]'' ensures that everything is ready for [[DNA]] synthesis.
|-
| style="height:50px" | [[S phase|Synthesis]]
| '''S'''
| align="left" width="500pt" | [[DNA replication]].
|-
| style="height:50px" | [[G2 phase|Gap 2]]
| '''G<sub>2</sub>'''
| align="left" width="500pt" | Growth and preparation for mitosis. The ''[[Cell cycle checkpoint#G2 Checkpoint|G<sub>2</sub> checkpoint]]'' ensures that everything is ready to enter the M (mitosis) phase and divide.
|-
| [[Cell division]]
| style="height:50px" | [[Mitosis]]
| '''M'''
|  align="left" width="500pt" | Cell division occurs. The ''[[Cell cycle checkpoint#Metaphase Checkpoint|Metaphase Checkpoint]]'' ensures that the cell is ready to complete cell division.
|}

===G<sub>0</sub> phase (quiescence)===
[[File:Plant cell cycle.svg|thumb|Plant cell cycle]]
[[File:Animal cell cycle-en.svg|thumb|Animal cell cycle]]
{{main|G0 phase}}

G<sub>0</sub> is a resting phase where the cell has left the cycle and has stopped dividing. The cell cycle starts with this phase. Non-proliferative (non-dividing) cells in multicellular [[eukaryote]]s generally enter the quiescent G<sub>0</sub> state from G<sub>1</sub> and may remain quiescent for long periods of time, possibly indefinitely (as is often the case for [[neuron]]s). This is very common for cells that are fully [[cellular differentiation|differentiated]]. Some cells enter the G<sub>0</sub> phase semi-permanently and are considered post-mitotic, e.g., some liver, kidney, and stomach cells. Many cells do not enter G<sub>0</sub> and continue to divide throughout an organism's life, e.g., epithelial cells.

The word "post-mitotic" is sometimes used to refer to both [[G0 phase|quiescent]] and [[Cellular senescence|senescent]] cells. Cellular senescence occurs in response to DNA damage and external stress and usually constitutes an arrest in G<sub>1</sub>. Cellular senescence may make a cell's progeny nonviable; it is often a biochemical alternative to the self-destruction of such a damaged cell by [[apoptosis]].

===Interphase ===
{{main|Interphase}}
Interphase represents the phase between two successive M phases. Interphase is a series of changes that takes place in a newly formed cell and its nucleus before it becomes capable of division again. It is also called preparatory phase or intermitosis. Typically interphase lasts for at least 91% of the total time required for the cell cycle.

Interphase proceeds in three stages, G<sub>1</sub>, S, and G<sub>2</sub>, followed by the cycle of mitosis and cytokinesis. The cell's nuclear DNA contents are duplicated during S phase.

====G<sub>1</sub> phase (First growth phase or Post mitotic gap phase)====
[[File:Human karyotype with bands and sub-bands.png|thumb|250px|Schematic [[karyogram]] of the human chromosomes, showing their usual state in the G<sub>0</sub> and G<sub>1</sub> phase of the cell cycle. At top center it also shows the chromosome 3 pair in [[metaphase]] (annotated as "Meta."), which takes place after having undergone [[DNA synthesis]] which occurs in the [[S phase]] (annotated as S) of the cell cycle.<br>{{further|Karyotype}}]]
{{main|G1 phase}}
The first phase within interphase, from the end of the previous M phase until the beginning of DNA synthesis, is called [[G1 phase|G<sub>1</sub>]] (G indicating ''gap''). It is also called the growth phase. During this phase, the biosynthetic activities of the cell, which are considerably slowed down during M phase, resume at a high rate. The duration of G<sub>1</sub> is highly variable, even among different cells of the same species.<ref name="pmid4515625">{{cite journal | vauthors = Smith JA, Martin L | title = Do cells cycle? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 70 | issue = 4 | pages = 1263–1267 | date = April 1973 | pmid = 4515625 | pmc = 433472 | doi = 10.1073/pnas.70.4.1263 | doi-access = free | bibcode = 1973PNAS...70.1263S }}</ref> In this phase, the cell increases its supply of proteins, increases the number of organelles (such as mitochondria, ribosomes), and grows in size. In G<sub>1</sub> phase, a cell has three options. 
*To continue cell cycle and enter [[S phase]]
*Stop cell cycle and enter [[G0 phase|G<sub>0</sub>]] phase for undergoing [[Cellular differentiation|differentiation]].
*Become arrested in G<sub>1</sub> phase hence it may enter G<sub>0</sub> phase or re-enter cell cycle. 
The deciding point is called [[Cell cycle checkpoint#G1 .28Restriction.29 Checkpoint|check point]] ([[Restriction point]]). This [[Cell cycle checkpoint#G1 .28Restriction.29 Checkpoint|check point]] is called the restriction point or START and is regulated by G<sub>1</sub>/S cyclins, which cause transition from G<sub>1</sub> to S phase. Passage through the G<sub>1</sub> check point commits the cell to division.

====S phase (DNA replication)====
{{main|S phase}}
The ensuing [[S phase]] starts when [[DNA synthesis]] commences; when it is complete, all of the [[chromosome]]s have been replicated, i.e., each chromosome consists of two sister [[chromatid]]s. Thus, during this phase, the amount of DNA in the cell has doubled, though the [[ploidy]] and number of chromosomes are unchanged. Rates of RNA [[Transcription (genetics)|transcription]] and [[Protein biosynthesis|protein synthesis]] are very low during this phase. An exception to this is [[histone]] production, most of which occurs during the S phase.<ref name="pmid7199388">{{cite journal | vauthors = Wu RS, Bonner WM | title = Separation of basal histone synthesis from S-phase histone synthesis in dividing cells | journal = Cell | volume = 27 | issue = 2 Pt 1 | pages = 321–330 | date = December 1981 | pmid = 7199388 | doi = 10.1016/0092-8674(81)90415-3 | s2cid = 12215040 }}</ref><ref name="pmid12370293">{{cite journal | vauthors = Nelson DM, Ye X, Hall C, Santos H, Ma T, Kao GD, Yen TJ, Harper JW, Adams PD | display-authors = 6 | title = Coupling of DNA synthesis and histone synthesis in S phase independent of cyclin/cdk2 activity | journal = Molecular and Cellular Biology | volume = 22 | issue = 21 | pages = 7459–7472 | date = November 2002 | pmid = 12370293 | pmc = 135676 | doi = 10.1128/MCB.22.21.7459-7472.2002 }}</ref><ref name="pmid14018040">{{cite journal | vauthors = Cameron IL, Greulich RC | title = Evidence for an essentially constant duration of DNA synthesis in renewing epithelia of the adult mouse | journal = The Journal of Cell Biology | volume = 18 | issue = 1 | pages = 31–40 | date = July 1963 | pmid = 14018040 | pmc = 2106275 | doi = 10.1083/jcb.18.1.31 }}</ref>

====G<sub>2</sub> phase (growth)====
{{main|G2 phase}}
G<sub>2</sub> phase occurs after DNA replication and is a period of protein synthesis and rapid cell growth to prepare the cell for mitosis. During this phase microtubules begin to reorganize to form a spindle (preprophase). Before proceeding to [[Mitosis|mitotic phase]], cells must be checked at the G<sub>2</sub> checkpoint for any DNA damage within the chromosomes. The G<sub>2</sub> checkpoint is mainly regulated by the tumor protein [[P53 upregulated modulator of apoptosis|p53]]. If the DNA is damaged, p53 will either repair the DNA or trigger the apoptosis of the cell. If p53 is dysfunctional or mutated, cells with damaged DNA may continue through the cell cycle, leading to the development of cancer.

===Mitotic phase (chromosome separation)===
<!--[[Mitotic phase]] and [[M phase]] redirect here-->
{{Main|Mitosis}}
The relatively brief ''M phase'' consists of nuclear division ([[karyokinesis]]) and division of cytoplasm ([[cytokinesis]]). M phase is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These phases are sequentially known as:
*[[prophase]]
*[[prometaphase]]
*[[metaphase]]
*[[anaphase]]
*[[telophase]]

[[Image:Mitosis Stages.svg|center|900px|A diagram of the mitotic phases]]
Mitosis is the process by which a [[eukaryotic]] cell separates the [[chromosome]]s in its [[cell nucleus]] into two identical sets in two nuclei.<ref>{{cite web | vauthors = Rubenstein I, Wick SM | title = Cell | website = World Book Online Reference Center | date = 2008 | url = http://www.worldbookonline.com/wb/Article?id%3Dar102240 | access-date = 2009-07-10 | url-status = dead | archive-url = https://web.archive.org/web/20110530132021/http://www.worldbookonline.com/wb/Article?id=ar102240 | archive-date = 30 May 2011}}</ref> During the process of mitosis the pairs of [[chromosomes]] condense ([[chromosome condensation]]) and attach to [[microtubule]]s that pull the [[sister chromatids]] to opposite sides of the cell.<ref name = "Maton_1997">{{cite book | vauthors = Maton A, Lahart D, Hopkins J, Warner MQ, Johnson S, Wright JD | title = Cells: Building Blocks of Life | publisher = Prentice Hall | year = 1997 | location = New Jersey | pages = [https://archive.org/details/cellsbuildingblo00mato/page/70 70–4] | isbn = 978-0-13-423476-2 | url = https://archive.org/details/cellsbuildingblo00mato/page/70 }}</ref>

Mitosis occurs exclusively in [[eukaryote|eukaryotic]] cells, but occurs in different ways in different species. For example, animal cells undergo an "open" mitosis, where the [[nuclear envelope]] breaks down before the chromosomes separate, while [[fungi]] such as ''[[Aspergillus nidulans]]'' and ''[[Saccharomyces cerevisiae]]'' ([[yeast]]) undergo a "closed" mitosis, where chromosomes divide within an intact [[cell nucleus]].<ref>{{cite journal | vauthors = De Souza CP, Osmani SA | title = Mitosis, not just open or closed | journal = Eukaryotic Cell | volume = 6 | issue = 9 | pages = 1521–1527 | date = September 2007 | pmid = 17660363 | pmc = 2043359 | doi = 10.1128/EC.00178-07 }}</ref>

===Cytokinesis phase (separation of all cell components)===
{{Main|Cytokinesis}}

[[File:Cytokinesis in animal cells and plant cells.jpg|thumb|Cytokinesis in animal cells and plant cells]]

Mitosis is immediately followed by [[cytokinesis]], which divides the nuclei, [[cytoplasm]], [[organelle]]s and [[cell membrane]] into two cells containing roughly equal shares of these cellular components. Cytokinesis occurs differently in plant and animal cells. While the cell membrane forms a groove that gradually deepens to separate the cytoplasm in animal cells, a [[cell plate]] is formed to separate it in plant cells. The position of the cell plate is determined by the position of a preprophase band of microtubules and [[actin]] filaments. Mitosis and cytokinesis together define the [[cell division|division]] of the parent cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 10% of the cell cycle.

Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "M phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei in a process called [[endoreplication]]. This occurs most notably among the [[fungus|fungi]] and [[slime mold]]s, but is found in various groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of [[Drosophila melanogaster|fruit fly]] embryonic development.<ref name=Lilly>{{cite journal | vauthors = Lilly MA, Duronio RJ | title = New insights into cell cycle control from the Drosophila endocycle | journal = Oncogene | volume = 24 | issue = 17 | pages = 2765–2775 | date = April 2005 | pmid = 15838513 | doi = 10.1038/sj.onc.1208610 | s2cid = 25473573 | doi-access =  }}</ref> Errors in mitosis can result in cell death through [[apoptosis]] or cause [[mutation]]s that may lead to [[cancer]].