G1 phase

The G ₁ phase, together with the S phase and G ₂ phase, constitutes a long period of cell growth — the interphase that precedes cell division — mitosis (M phase) ^[1] .

During the G ₁ phase, the cell grows in size and synthesizes mRNA and proteins necessary for DNA synthesis. When the cell reaches the required size, and the necessary proteins have already been synthesized, the cell enters the next phase of the cell cycle - the S-phase. The duration of each phase, including the G ₁ phase, differs in different types of cells. In human somatic cells , the cell cycle lasts about 18 hours, and about a third of this time falls on the G ₁ phase ^[2] . However, in the embryos of the Spur frog ( Xenopus ), sea ​​urchins ( Echinoidea ) and Drosophila ( Drosophila ), the G ₁ phase is weakly expressed and represents the gap, if any, between the end of mitosis and the S phase ^[2] .

The G ₁ phase and other phases of the cell cycle may depend on growth factors , such as nutrients , temperature, and growth spaces. A sufficient number of amino acids must be present for the synthesis of mRNA and proteins. Physiological temperatures are optimal for cell growth. In humans, the normal physiological temperature is about 36.5 ° C (under the arm) ^[1] .

The G ₁ phase is especially important for the cell cycle, because during this period the cell determines whether it will divide or leave the cell cycle ^[2] . If the cell remains non-dividing instead of going into the S phase, it leaves the G ₁ phase and goes into a state of rest called the G ₀ phase . It is difficult, but possible to return to the G ₁ phase from the G ₀ phase ^[1] .

Throughout the G ₁ phase, the cell remains diploid ( 2n ). This means that the cell contains a double set of chromosomes specific for this species, and the DNA has not yet been replicated before cell division . The genetic material is in the form of chromatin or weakly helical DNA chains. Haploid eukaryotic organisms , for example, some yeast , have only one set of chromosomes ( 1n ). During the G ₁ phase, the cell is still preparing for DNA replication , and its genetic material has not yet been copied (this occurs in the S phase) ^[1] .

There is a clear set of instructions in the cell cycle, known as the cell cycle control system, which controls the duration and coordination of the phases of the cell cycle to ensure the correct order of their course. Biochemical triggers known as cyclin-dependent kinases trigger cell-type steps at the right time and provide the correct order to prevent errors ^[2] .

There are three control points in the cell cycle: G ₁ / S-control point (transition from G ₁ -phase to S-phase) or the starting point in yeast, G ₂ / M-control point and spindle point ^[1] .

Biochemical G ₁ Phase Regulators

During the G ₁ phase, the activity of G ₁ / S cyclins increases significantly towards the end of the G ₁ phase. These cyclins initiate some early processes associated with cell division, such as centrosome doubling in vertebrates, spindle formation in yeast, but for the most part they are responsible for the activation of S-cyclin complexes ^[2] .

Complexes of cyclins active in other phases of the cell cycle are in an inactive state in this phase so that the corresponding cellular processes do not go in the wrong order. In the G ₁ phase, there are three ways to suppress the activity of cyclin-dependent kinases: inhibitor genes inhibit the translation of major cyclin genes by regulatory proteins; anaphase stimulation complex is activated, which directionally suppresses S- and M-cyclins (but not G ₁ / S-cyclins) and, finally, a high concentration of cyclin-dependent kinase inhibitors ^[2] .

Restriction point

In the G ₁ phase , the restriction point (R) differs from the rest of the control points, because it does not determine the special state of the cell, ideal for the transition to the next phase, but changes the further direction of cell life. In vertebrates, after the cell has been in the G ₁ phase for about three hours, it enters the restriction point, where the cell decides whether it will go further along the cell cycle or will enter the resting stage, the G ₀ phase ^[3] .

This point also divides the G ₁ phase into two halves: premitotic and postmitotic. Between the onset of the G ₁ phase (which begins in a new cell after mitosis) and the R cell is in the G ₁ postmitotic subphase or postmitotic phase. After R and before the S-phase, the cell is called being in the G ₁ -synthetic subphase or presynthetic phase of the G ₁ -phase ^[4] .

For the cell to pass through the G ₁ -postmitotic phase, a high content of growth factors and a stable level of protein synthesis are necessary, otherwise the cell will transfer to the G ₀ phase ^[4] .

Some authors argue that the restriction point and the G ₁ / S-point are one and the same ^{[1] [2]} , but in newer works it turned out that these are two different points of the G ₁ -phase in which cell progress is noted. The first, the restriction point, depends on growth factors and determines whether the cell goes into the G ₀ phase, while the second control point depends on nutrients and determines whether the cell goes into the S phase ^{[3] [4]} . Some disagreements between the researchers attribute to the fact that some of them studied mammalian cells, while others studied yeast ^[3] .

G ₁ / S-control point

The G ₁ / S control point is between the beginning of the G ₁ phase and the S phase, in which the transition of the cell into the S phase is determined. Factors due to which the cell may not enter the S-phase may be a lack of growth factors, DNA damage and other special circumstances.

At this point, the formation of a complex of G ₁ / S-cyclins and cyclin-dependent kinases (CZK) leads the cell to enter a new division cycle. Then these complexes activate S-CZK complexes, which lead the cell to DNA replication in the S phase. At the same time, the activity of the anaphase stimulation complex is significantly reduced, which allows S- and M-cyclins to be activated.

If the cell cannot pass into the S phase, it enters the resting G ₀ phase, where there is neither cell growth nor division ^[1] .

Many sources confirm that abnormalities in the G ₁ phase and the G ₁ / S control point lead to uncontrolled tumor growth. In cases where the disturbances affect the G ₁ phase, this is mainly because the genes encoding regulatory proteins of the E2F family acquire unlimited activity and increase the expression of G ₁ / S cyclin genes, as a result of which the cell uncontrolled again and again enters cell cycle ^[2] .

However, drugs against some forms of cancer also act on the G ₁ phase of the cell cycle. In many types of cancer , including breast cancer ^[5] and skin cancer ^[6] , tumor growth can be prevented by preventing tumor cells from entering the G ₁ phase, preventing cell division and proliferation.