Editing G1 phase

{{short description|First growth phase in the eukaryotic cell cycle}}
{{DISPLAYTITLE:G<sub>1</sub> phase}}
[[File:Animal cell cycle-en.svg|right|thumb|350px|Mitosis in an [[animal cell]] (phases ordered counter-clockwise), with G<sub>1</sub> labeled at left.]]
The '''G<sub>1</sub> phase''', '''gap 1 phase''', or '''growth 1 phase''', is the first of four phases of the [[cell cycle]] that takes place in [[eukaryotic cell]] division. In this part of [[interphase]], the cell synthesizes [[Messenger RNA|mRNA]] and [[proteins]] in preparation for subsequent steps leading to mitosis. G<sub>1</sub> phase ends when the cell moves into the [[S phase]] of interphase. Around 30 to 40 percent of cell cycle time is spent in the G<sub>1</sub> phase.

== Overview ==
[[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}}]]
G<sub>1</sub> phase together with the [[S phase]] and [[G2 phase|G<sub>2</sub> phase]] comprise the long growth period of the [[cell cycle]] [[cell division]] called [[interphase]] that takes place before [[cell division]] in [[mitosis]] (M phase).<ref name=Lodish>{{cite book | first1 = Harvey | last1 = Lodish | first2 = Arnold | last2 = Berk | first3 = S Lawrence | last3 = Zipursky | first4 = Paul | last4 = Matsudaira | first5 = David | last5 = Baltimore | first6 = James | last6 = Darnell | name-list-style = vanc | title = Molecular cell biology | isbn = 978-0-7167-3136-8 | edition = 4th | url = https://archive.org/details/molecularcellbio00lodi | date = 2000 | location = New York | publisher = W. H. Freeman | url-access = registration }}</ref>

During G<sub>1</sub> phase, the cell grows in size and synthesizes [[mRNA]] and [[protein]] that are required for [[DNA]] synthesis. Once the required proteins and growth are complete, the cell enters the next phase of the cell cycle, S phase. The duration of each phase, including the G<sub>1</sub> phase, is different in many different types of cells. In human somatic cells, the  G<sub>1</sub> stage of the cell cycle lasts about 10 hours.<ref name=Morgan>{{cite book | last = Morgan | first = David | title = The Cell Cycle: Principals of Control | location = London | publisher = New Science Press LTD | date = 2007 }}</ref> However, in [[Xenopus]] embryos, [[sea urchin]] embryos, and [[Drosophila]] embryos, the G<sub>1</sub> phase is barely existent and is defined as the gap, if one exists, between the end of mitosis and the S phase.<ref name=Morgan />

G<sub>1</sub> phase and the other subphases of the cell cycle may be affected by limiting [[growth factors]] such as nutrient supply, temperature, and room for growth. Sufficient [[nucleotides]] and [[amino acids]] must be present in order to synthesize mRNA and proteins. Physiological temperatures are optimal for cell growth. In humans, the normal physiological temperature is around [[human body temperature|37 °C]] (98.6&nbsp;°F).<ref name= Lodish />

G<sub>1</sub> phase is particularly important in the cell cycle because it determines whether a cell commits to division or to leaving the cell cycle.<ref name= Morgan /> If a cell is signaled to remain undivided, instead of moving onto the S phase, it will leave the G<sub>1</sub> phase and move into a state of dormancy called the [[g0 phase|G<sub>0</sub> phase]]. Most nonproliferating vertebrate cells will enter the G<sub>0</sub> phase.<ref name= Lodish />

== Regulation ==

Within the cell cycle, there is a stringent set of regulations known as the [[cell cycle|cell cycle control system]] that controls the timing and coordination of the phases to ensure a correct order of events. Biochemical triggers known as [[cyclin-dependent kinases]] (Cdks) switch on cell cycles events at the corrected time and in the correct order to prevent any mistakes.<ref name=Morgan />

There are three checkpoints in the cell cycle: the '''G<sub>1</sub>/S Checkpoint''' or the '''Start checkpoint''' in yeast; the [[G2 phase|G<sub>2</sub>/M checkpoint]]; and the [[spindle checkpoint]].<ref name=Lodish />

===Biochemical regulators===
{{Main|Cyclin E1}}

During G<sub>1</sub> phase, the G<sub>1</sub>/S cyclin activity rises significantly near the end of the G<sub>1</sub> phase.

Complexes of cyclin that are active during other phases of the cell cycle are kept inactivated to prevent any cell-cycle events from occurring out of order. Three methods of preventing Cdk activity are found in G<sub>1</sub> phase: [[Retinoblastoma protein|pRB]] binding to [[E2F]] family transcription factors downregulate [[Gene expression|expression]] of S phase cyclin genes; [[anaphase-promoting complex]] (APC) is activated, which targets and degrades S and M cyclins (but not G<sub>1</sub>/S cyclins); and a high concentration of Cdk inhibitors is found during G<sub>1</sub> phase.<ref name=Morgan />

===Restriction point===

{{Main|Restriction point}}

The [[restriction point]] ('''R''') in the G<sub>1</sub> phase is different from a checkpoint because it does not determine whether cell conditions are ideal to move on to the next phase, but it changes the course of the cell. After a vertebrate cell has been in the G<sub>1</sub> phase for about three hours, the cell enters a restriction point in which it is decided whether the cell will move forward with the G<sub>1</sub> phase or move into the dormant G<sub>0</sub> phase.<ref name=Foster>{{cite journal | vauthors = Foster DA, Yellen P, Xu L, Saqcena M | title = Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient-Sensing Cell Growth Checkpoint(s) | journal = Genes & Cancer | volume = 1 | issue = 11 | pages = 1124–31 | date = November 2010 | pmid = 21779436 | pmc = 3092273 | doi = 10.1177/1947601910392989 }}</ref>

This point also separates two halves of the G<sub>1</sub> phase; the post-mitotic and pre-mitotic phases. Between the beginning of the G<sub>1</sub> phase (which is also after mitosis has occurred) and R, the cell is known as being in the G<sub>1</sub>-pm subphase, or the post-mitotic phase. After R and before S, the cell is known as being in G<sub>1</sub>-ps, or the pre S phase interval of the G<sub>1</sub> phase.<ref name=Zetterberg>{{cite journal | vauthors = Zetterberg A, Larsson O, Wiman KG | title = What is the restriction point? | journal = Current Opinion in Cell Biology | volume = 7 | issue = 6 | pages = 835–42 | date = December 1995 | pmid = 8608014 | doi = 10.1016/0955-0674(95)80067-0 }}</ref>

In order for the cell to continue through the G<sub>1</sub>-pm, there must be a high amount of growth factors and a steady rate of protein synthesis, otherwise the cell will move into G<sub>0</sub> phase.<ref name=Zetterberg />

==== Conflicting research ====
Some authors will say that the restriction point and the G<sub>1</sub>/S checkpoint are one and the same,<ref name=Lodish /><ref name=Morgan /> but more recent studies have argued that there are two different points in the G<sub>1</sub> phase that check the progression of the cell. The first restriction point is growth-factor dependent and determines whether the cell moves into the G<sub>0</sub> phase, while the second checkpoint is nutritionally-dependent and determines whether the cell moves into the S phase.<ref name=Foster /><ref name=Zetterberg />

===The G<sub>1</sub>/S checkpoint===

{{Main|Cell cycle checkpoint}}

The '''G<sub>1</sub>/S checkpoint''' is the point between G<sub>1</sub> phase and the S phase in which the cell is cleared for progression into the S phase. Reasons the cell would not move into the S phase include insufficient cell growth, damaged DNA, or other preparations have not been completed.

At the G<sub>1</sub>/S checkpoint, formation of the G<sub>1</sub>/S cyclin with Cdk to form a complex commits the cell to a new division cycle.<ref name=Morgan /> These complexes then activate S-Cdk complexes that move forward with [[DNA replication]] in the S phase. Concurrently, [[anaphase-promoting complex]] (APC) activity decreases significantly, allowing S and M cyclins to become activated.

If a cell does not clear to pass through to the S phase, it enters the dormant G<sub>0</sub> phase in which there is no cellular growth or division.<ref name=Lodish />

==In cancer==

{{Main|Cell cycle#Role in tumor formation|l1=Cell cycle role in cancer}}

Many sources have linked irregularities in the G<sub>1</sub> phase or the G<sub>1</sub>/S checkpoint to uncontrolled growth of [[tumors]]. In these cases where the G<sub>1</sub> phase is affected, it is generally because [[Regulation of gene expression|gene regulatory proteins]] of the [[E2F]] family have become unrestrained and increase G<sub>1</sub>/S cyclin gene expression, leading to uncontrolled cell-cycle entry.<ref name=Morgan />

However, the cure for some forms of cancer also lies in the G<sub>1</sub> phase of the cell cycle. Many cancers including [[breast cancer|breast]]<ref>{{cite journal | vauthors = Wali VB, Bachawal SV, Sylvester PW | title = Combined treatment of gamma-tocotrienol with statins induce mammary tumor cell cycle arrest in G1 | journal = Experimental Biology and Medicine | volume = 234 | issue = 6 | pages = 639–50 | date = June 2009 | pmid = 19359655 | doi = 10.3181/0810-RM-300 | s2cid = 30323288 }}</ref> and [[skin cancer|skin]] cancers <ref>{{cite journal | vauthors = Ye Y, Wang H, Chu JH, Chou GX, Chen SB, Mo H, Fong WF, Yu ZL | title = Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells | journal = Journal of Ethnopharmacology | volume = 136 | issue = 1 | pages = 279–82 | date = June 2011 | pmid = 21524699 | doi = 10.1016/j.jep.2011.04.020 }}</ref> have been prevented from proliferating by causing the tumor cells to enter G<sub>1</sub> cell cycle arrest, preventing the cells from dividing and spreading.

== See also ==
* [[G1/S transition|G<sub>1</sub>/S transition]]

== References ==
{{reflist}}

{{Cell cycle}}

{{DEFAULTSORT:G1 Phase}}
[[Category:Cell cycle]]