In this post, we will discuss what happens in the G1 Phase and the G2 Phase of the cell cycle. Cell division entails making more cells through duplication of the cell’s contents and then splitting this cell into two identical cells. These cells are identical to the parent cell. This is how we grow and replace injured cells.

Introduction to G1 and G2 Phases

The key to a successful cell division is keeping the resulting cells identical. Maintaining the integrity of the cell and the DNA is central to the survival of species. Many organisms perish due to lethal mutations resulting from compromised DNA integrity.

The importance of DNA integrity lies in the number of quality checks that occur during the cell cycle. Cells have these checkpoints in place to ensure that they can successfully reproduce when they should. Cells go through the cell cycle and these checkpoints to ensure that each cell divides in perfect condition. The cell cycle has two major phases, the mitotic phase, and the interphase.

Interphase

Interphase is the longest phase of the cell cycle. Cell growth is central to the cell cycle, and this is the primary purpose of interphase. At the end of this phase, there is double the amount of DNA, centrioles have replicated, and the cell is big enough for cell division. Interphase consists of the first growth (G1 phase), Synthesis (S phase), and the second growth (G2 phase) phases (figure 1). The growth phases are, as you may have suspected, for the growth of the cell. During the synthesis phase, DNA replication occurs in preparation for the second growth phase.

Here we will take a look at the G phases (first and second growth) of the interphase. We will look at what happens at these phases, what follows, and why they are so important to understanding biology.

What Happens in the G1 Phase of the Cell Cycle?

In some instances, such as when a tissue has reached its target size, cells exit the cell cycle and stay in stasis called G0 (figure 1). Most of these cells are capable of re-entering the cell cycle at the G1 phase should the need ever arise. Nerve cells do not normally regenerate; they remain in stasis.

During the G1 phase, cells accomplish most of their growth. They get bigger in size and make proteins and organelles needed for normal functions of DNA synthesis. Here, proteins and RNAs are synthesized, and, more especially the centromere and the other components of the centrosomes are made. The cells are fully functional. In addition to being on a dividing mission, they can also perform their normal functions. In vertebrates and diploid yeasts, the chromosome number is 2n at this phase. Meanwhile, in haploid yeasts, the chromosome number is 1n.

In short, the first growth phase is the time when just after birth (in mitosis) the cell is preparing for DNA synthesis (in S phase).

What Happens in the G2 Phase of the Cell Cycle?

So far, we have looked at what happens in the first G1 phase. We also review what happens in the S phase in the article “What happens in the S-Phase”. Now let us take a quick trip through the second growth phase, the G2 phase.

The second growth phase follows the S phase (synthesis). Past the S phase, the cell goes through a quality control point where the integrity of the DNA is checked. After this, the cell enters the second growth phase where the nuclear envelope envelopes the nucleus. In this phase two centrosomes have formed (courtesy of the first growth phase); in animal cells, these centrosomes have two centrioles.

It is important to note that the DNA replicated in the S phase has not condensed into chromosomes yet. The organelles necessary for the cell division (in M phase) are also synthesized in the S phase. The microtubules that will be used to mobilize the chromosomes in M phase are assembled at G2.

Now, all of the tasks accomplished during G2 can only be properly achieved if the events before G2 have gone as planned. Pit stops termed checkpoints are present for the sole purpose of ensuring that the cell has successfully finished all each task before moving to the next phase. The cell cycle comprises three checkpoints, namely, M/G1 (Exit M), G1/S (Enter S) and G2/M (Enter M).

Checkpoints

The Exit M Checkpoint

Before the cell enters the G1 phase of the interphase, it goes through the Exit M checkpoint. Here the cell checks to ensure that it has completed the mitosis phase and is ready for the first growth phase. Specifically, cells check to see if they have completed the cell division and if the chromosomes have aligned properly and are attached to spindles.

The Enter S Checkpoint

Before the cell commits to the S phase, it goes through the G1/S checkpoint. This Enter S checkpoint checks the nutritional status of the cell and the DNA integrity. This is an especially important step for a cell about to enter the S phase. In yeast, the cell size is used as a proxy to determine if it is ready to go through to the next phase.

The Role of Proteins

When and how cells progress through the cell cycle is tightly controlled by a plethora of regulatory proteins. These proteins fall into two groups called cyclins and cyclin-dependent kinases (Cdks). The activity of the Cdks fluctuates along with the cyclins. Cyclins are proteins that regulate the timing of the cell cycle. Their levels fluctuate in the cell cycle, hence their name.

Late in mitosis, Cdc14 (a phosphatase) is held hostage in nucleoli. This prevents the activation of APC specificity factor (Cdh1) which is necessary to polyubiquitinate downstream cyclins. This prevents the necessary decrease in the activity of the maturation-promoting factor (a cyclin/CDK complex) which halts progression into telophase.

The telophase is prolonged long enough to check that chromosomes have segregated properly. Once this is confirmed, Cdc14 gets released. The associated downstream cascade leads to lowered levels of the MPF which prompts the progression of the cell past telophase, exiting the mitosis phase and going into G1. Everything that happens in the telophase and the resulting cytokinesis is what we refer to as an exit from mitosis.

The G1 checkpoint seems to be the determinant of the cell’s fate in the cell cycle. If a cell gets the green light at the G1 checkpoint, it usually makes the rounds (completing the cycle and dividing). Otherwise, it exits the cycle altogether, entering the G0 phase.

Enter M and the Regulation of the G2 Phase

The Enter M checkpoint influences the exit out of the G2 phase. At every transition of the cell cycle, the cells are continuously checked for DNA integrity, where (in the case of the S into G2 transition) the newly duplicated DNA is checked for mutations and fixed if necessary. Once this transition phase is passed the cell is ready for the G2 phase. Cyclins and the cyclin-dependent kinases (CDKs) complexes also control the transitions here, much like in G1.

The activity of cyclins and their CDKs is regulated through phosphorylation (by a CDK-activating Kinase; CAK) and dephosphorylation (by a phosphatase KAP) of specific residues (usually tyrosine) of the ATP-binding site of the CDKs.

The control of the Enter M checkpoint is mostly similar across eukaryotes, with most cyclins and their CDKs having homologs across different eukaryotic groups.

Example

Here we will focus on the fission yeast (Schizosaccharomycespombe) as an example. Four proteins are involved in the regulation of the protein kinase activity of the CDK in fission yeast in the control of entry into mitosis. Before we continue, it is worth noting that fission yeast has only one CDK while vertebrates have a family of CDKs.

In fission yeast, the mitotic cyclin, Cdc13, forms a complex with CDK to form maturation promoting factor (MPF). The protein-tyrosine kinase called Wee1 acts as an inhibitor of this complex by phosphorylating the tyrosine 15 of the CDK subunit. Then a CAK phosphorylates and activates threonine 161. This dual phosphorylation inactivates the MPF, delaying the progression of the cell from G2 into M phase. A phosphatase, Cdc25, comes along and dephosphorylates tyrosine, thereby activating the MPF. The highly active MPF can now relieve the cell and move it along into the mitotic phase.

Once again the cell goes into mitosis, diving and then going into G1. Here, the same question is asked again, “is the cell fated for another cell cycle trip or should it exit?” Once the decision is made, the cell goes through or gets out.

How is the G1 Phase Different from the G2 Phase?

We hope you already gauged this from the sections above. Here is the gist of it, the whole of interphase encompasses cell growth and cell division, this we know. One significant difference between growth phases is that the first growth phase is about cell growth while G2 is about cell division. It is important to fully grasp the roles of these gaps (outlined above).

Why are G1 and G2 Phases of Interphase so Important in our Understanding of Biology?

The cell cycle’s primary purpose is cell division. If the growth phases do not fulfill their roles, then the cell would be halved at every cell division until there is nothing to divide. This is because DNA replication would not be successfully achieved without the necessary proteins and organelles synthesized in the first growth phase.

Understanding the Cell Cycle’s Role In Cancer

To emphasize how important these phases are we will take a look at what happens if they go wrong. One famous example of a cell cycle gone wrong is cancer. Simply put, cancer is unchecked cell growth. In cancer, the cells lose their ability to tell when they are damaged and should exit the cycle and, preferably, go through apoptosis (programmed cell death).

Cancer results from defects in the cell cycle control (tumor suppressors and proto-oncogenes). If tumor suppressors fail to slow down the cell cycle for cell integrity checks, then the cell may proceed into DNA synthesis before it is ready, resulting in faulty DNA replication.

For a cell to go through DNA replication before it is ready would be disastrous. How so, you ask? The proteins that control the timing of the cell cycle are coded for by the DNA. Thus, if something goes wrong in replication, mistakes are likely to accumulate and potentially affect many other coding regions among which can be other regions coding for even more regulators. This would lead to the cell cycle going completely out of order, leading to proliferating tumor cells. If these damaged cells invade other organs or tissues, they can result in death of the affected individual.

The Importance of the Gap Phases

Now that we have gone through the overall gloom and doom let us focus on a specific problem—the failure of G1. First off, the G1 decides when a cell can divide based on environmental conditions, health, and cell size. Should this decision be taken away, the cell’s health would go unchecked, and, once again, damaged cells going through to S phase before they are ready.

Let us assume that the cell proceeds through the first growth phase just fine but bumps into an obstacle at G2. This would mean the microtubules, for example, do not assemble here, meaning the chromosomes are not mobilized. This would most likely lead to non-disjunction and, therefore, to cells with an unequal number of chromosomes.

The gaps (1 and 2) are essential for safeguarding DNA replication and mitosis. How so, you ask? Let us return to DNA replication gone wrong if replicating DNA gets into condensation before it’s ready it breaks. Also, if replication occurs just before mitosis, then you get unequal separation of genetic material. Thus it is important to keep replication and mitosis separated by the G phases to prepare the cells. DNA replication and mitosis are such important events that having the chance G phases and checkpoints) to check the integrity of the cell before these events happen is a necessary precaution.

Understanding what happens in these phases is central to our understanding of what goes wrong in cancer.

Conclusion

This is an introductory Biology overview of the G phases of the cell cycle; it is by no means an exhaustive cover of this complex subject matter. The cell cycle is a vital part of the existence of all eukaryotes. As such it is important for it to be tightly controlled (by tumor suppressors and proto-oncogenes).

The growth phases are, perhaps, the most critical phases of the cell cycle. What happens in the G1 phase of the cell cycle? G1 phase prepares the cells fresh out of mitosis for another round of DNA replication by making the necessary proteins and organelles. G1 and G2, although both are growth phases are different. So, what happens in the G2 phase of the cell cycle? The second growth phase starts to prepare the cells with newly replicated DNA for entry into the mitosis phase by putting in place the necessary organelles for mitosis.

The cell cycle is a vital part of the continued persistence of all eukaryotes and prokaryotes.

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