Editing G1 phase (section)

== 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 />