Introduction

Multicellular organisms like humans are made up of millions of cells. These cells go through multiple stages during their life, collectively called the cell cycle. The mitotic cycle is a type of cell cycle in which cell division takes place by the process of mitosis.

The mitotic cell cycle is essential for making new daughter cells from the parent cells. The new cells are essential to replace the older worn-out cells that are not performing their function to the fullest. This process represents the process of reproduction at a much lower level.

The cell cycle is divided into a number of phases. Details of each phase will be discussed in this article. We will also discuss different regulatory mechanisms that ensure the smooth transition of cells from one phase to the next. So, keep reading.

Stages of Cell Cycle

A cell cycle can be defined as a sequence of events that ultimately result in the division of cells. It includes the following four stages:

• G1 phase
• S phase
• G2 phase
• M phase

In the first three stages, the cell prepares itself to undergo division. In the last phase, the M phase, the cell actually undergoes division and gives rise to daughter cells. The cell may undergo mitosis or meiosis during the M phase, depending on the type of cell.

The portion of the cell cycle before the M phase is also sometimes called Interphase.

Another phase called the G0 phase is also seen in the case of some cells. It is the quiescent phase. Cells that enter the G0 phase do not undergo any division. Details will be discussed under the subsequent heading.

G1 Phase

This phase of the cell cycle is also called growth phase 1. It is the first phase in the life cycle of any eukaryotic cell. The interphase begins with this stage of the cell cycle. Once a cell is made in the M phase, it immediately enters the G1 phase.

It is the stage during which a cell grows in size, makes proteins, and mRNA. All these changes are needed for the next stages of the cell cycle.

Cell Growth

It should be kept in mind that a cell enters the G1 phase as soon as it is formed. Thus, the cell is immature and very small in size. During the G1 phase, the cell synthesizes organelles, cytoplasmic contents, etc. All these factors lead to a maturing cell that is increasing in its size. At the end of the G1 phase, a cell is much larger than it was at the beginning of the cell cycle.

Synthesis of mRNA

Another important event that occurs during the G1 phase is the synthesis of mRNA. The mRNA molecules are the working copies of DNA. The information present in different genes in the form of DNA within the nucleus is copied in the form of mRNA. The process by which mRNA is formed is called transcription.

Transcription is the process during which the nucleotide sequence of DNA strand is read by RNA polymerase enzyme a complementary sequence is made in the form of mRNA. The enzyme copies the nucleotide sequence of the coding strand in the form of the nucleotide sequence in mRNA.

The mRNA molecules are made within the nucleus. Later, they move via the nuclear pores into the cytoplasm. Here, they are attached by ribosomes and the nucleotide sequence is translated into the sequence of amino acids within the polypeptides.

Protein Synthesis

Proteins are made by the process of translation. The mRNA molecules that are also made during this phase of the cell cycle carry the information for protein synthesis.

Each mRNA molecule is a single strand of nucleotides. Three nucleotides carry information about one amino acid in the polypeptide chain that is to be synthesized. This sequence of three nucleotides is called a codon. At a time, only one codon is expressed on the surface of the ribosome.

The tRNA molecules carry the amino acids to the site of protein synthesis. They get attached to the codon that is exposed. A peptide bond is formed between the new amino acid and the previous peptide chain. In this way, new amino acids keep adding and the chain continues to grow.

Proteins formed during this phase of the cell cycle are essential for the rest of the stages. These include various enzymes that are used in the subsequent phase of the mitotic cell cycle.

Regulation

All the stages of the cell cycle are strictly regulated to ensure integrity. It makes sure that the cell does not enter the next stage of the cell cycle before completing the previous one.

During the G1 phase, the cell passes through a point called the restriction point or R point. It determines whether the cell will continue to go through the rest of the stages of the cell cycle or simply enter a silent G0 phase.

If a cell remains in the G1 phase for more than 3 hours, it enters the restriction phase from where it passes to the G0 phase. Such cells do not undergo any division later on.

The R point also divides the G1 phase into two halves:

• G1 phase before the R point is called post-mitotic phase
• G1 phase after the R point is called the pre-S phase

G1/S checkpoint

During the cell cycle, the transition from one stage to the next is regulated by various checkpoints. G1/S checkpoint is the first one. During this checkpoint, the decision is made whether the cell is ready to move into the S phase or not.

If the cell has not grown sufficiently or has damaged DNA, it will not be cleared for the next stage.

If all the preparations have been made, the level of G1/S cyclins rises, and they cause the cell to move past this checkpoint into the S phase.

G0 Phase

It is not a part of a normal cell cycle. Cells that do not undergo division enter the G0 phase.

Earlier, it was thought that all the cells go through the four stages of the cell cycle. Later, some radioactive studies showed that it is not the case with all the cells. Some cells opt to nor undergo any replication and enter a silent stage called the G0 phase.

It was thought that the cell used to enter the G0 phase due to some environmental factors such as lack of nutrients, abnormal conditions for cell replication etc. Later studies confirmed that it is not the case. Some cells opt to enter the G0 phase even when the environment is favourable for replication. For example, neurons cells in an adult human being are in the G0 phase despite the fact that they are receiving all the nutrients and are metabolically active.

G0 phase may be reversible or irreversible.

Reversible

In the case of the reversible G0 phase, cells enter the silent phase due to the absence of some growth signals or some other environmental factors. When such cells receive the signal for replication, they leave the G0 phase and continue the normal cell cycle.

Liver cells are an example of cells that enter the reversible G0 phase.

Irreversible

In this case, cells reside in the G0 phase for an unlimited period of time. They cannot re-enter the normal cell cycle. Such cells either have abnormal DNA or enter the G0 phase as a developmental process as they are fully mature and differentiated and cannot undergo replication.

An example is neuron cells in adults.

S Phase

It is the second phase in the normal mitotic cell cycle. The S phase is also called the synthetic phase. During this stage of interphase, a cell undergoes DNA replication. Two copies of DNA are made during this stage. As a result, the chromosome number also doubles.

The different events that occur during the S phase are as follows.

DNA Replication

It is the most crucial event that occurs during the S phase. It is the process during which two identical copies of DNA are made.

DNA replication begins at specific sites of DNA strands called the replication origins. During the S phase, the two strands of DNA are unwound at these origin sites and a replication fork is formed. Once the replication fork is formed, certain enzymes necessary for DNA replication arrive at the replication site.

A primer is made by the primase enzyme. The DNA polymerase enzyme attaches the primer and starts making complementary daughter DNA strands by combining the nucleotides.

At the end of the replication process, two copies of double-stranded DNA are formed. Each newly formed DNA contains one parent (old) strand and one daughter (newly made) strand.

Histone Synthesis

The newly formed DNA also needs to be packed into chromosomes for the cell cycle to continue. Histones are specific proteins that bind the double-stranded DNA to form nucleosomes. It is the first step in the packaging of DNA.

Since new DNA is formed, new histone proteins are also needed. The synthesis of histone proteins also takes place during the S phase. These proteins are made in the cytoplasm and are then channelled into the nucleus via nuclear pores.

Nucleosome Replication

New histone proteins formed during the S phase get attached to the DNA to form nucleosomes. The nucleosomes are formed just behind the replication fork. As the replication fork continues to move forward, the newly made DNA is attached with histone proteins to make nucleosomes.

There is a dispute about the model of nucleosome replication. Some studies show that the old and the newly synthesized histone proteins remain completely segregated. No nucleosome contains a combination of old and new histone. They contain either all the newly made histone proteins, or all previous parent histones.

Regulation

As mentioned earlier, the entry of cells into the S phase is scrutinized by the G1/S checkpoint.

During the S phase, the cell also goes through some checkpoints that basically ensure that the DNA replication process has been completed without any error.

The three important checkpoints during the S phase are as follows.

Replication Checkpoint

It makes sure that there are no arrested replication forks in the DNA. If the replication is arrested at any of the replication forks, it causes a cellular signal to increase the availability of nucleotides to complete the replication process.

S-M Checkpoint

This checkpoint keeps the mitosis or cell division blocked until the entire genetic material has been copied.

Intra S Phase Checkpoint

It detects any errors in replication and damaged DNA such as double-strand breaks. It also signals the cell to start DNA repairing mechanisms so that the cell cycle can be continued after repairing the DNA.

G2 Phase

It is also called the second growth phase. It is the third stage of the cell cycle and the last stage for interphase. The cell replication or mitosis begins immediately after this phase.

During this phase of the cell cycle, the cell prepares itself for mitosis. The important events that occur during this phase are as follows.

Cell Growth

This phase is much similar to the first growth phase. Just like the G1, cells in the G2 phase further increase in size due to the synthesis of organelles and cytoplasmic content. The cell achieves its ideal size at the end of the G2 phase.

Protein Synthesis

New proteins are made by the process of translation as mentioned in the G1 phase. Here, the main focus is on the synthesis of proteins that will be needed during the next phase, mitosis.

These include the synthesis of fibrous proteins as well as enzymes that will be needed during the process of mitosis.

DNA Repair

Recall that new copies of DNA have been synthesized in the S phase. The double-strand breaks recognized at the inter S phase checkpoint can be repaired during the G2 phase, prior to the beginning of the M phase.

Regulation

If the G2 phase has been completed properly, cyclin-B1 levels tend to rise in the cell. it binds to CDK and the cell moves into the M phase.

However, if the cells have damaged DNA or failed to replicate the chromosomes, they are arrested in the G2 phase. Such cells do not make it into the M phase.

M Phase

It is the last phase in the cell cycle. During this phase, the cell replication is completed by the formation of two daughter cells.

It involves two divisions:

• Division of nucleus called karyokinesis
• Division of cytoplasm called cytokinesis

Karyokinesis is divided into the following four phases:

• Prophase
• Metaphase
• Anaphase
• Telophase

The details of all these phases are given below.

Prophase

It is a preparatory phase during which nuclear material is arranged for division. During the prophase, chromatin material within the nucleus arranges itself in the form of chromosomes. The chromosomes become tightly packed, and the gene transcription stops. It is during this phase that the chromosomes are visible inside the nucleus under a microscope.

As the chromosomes become more apparent towards the end of the prophase, the nuclear envelope also undergoes degradation.

Centrosomes are the structures responsible for making mitotic spindles during mitosis. They start making the mitotic spindle and get pushed to the opposite poles of the nucleus towards the end of the prophase.

At the end of the prophase, the nucleus disappears. It gets replaced by the chromosomes and early mitotic apparatus between two centrosomes.

Pre-prophase

This is seen in plant cells in which the nucleus is pushed to one side of the cell. During this phase, the nucleus is brought to the centre of the cell so that mitosis can take place.

Pro-metaphase

It is a phase between the prophase and metaphase. During this phase, the nuclear envelope disappears completely, and the centrosomes get migrated to the opposite poles. The spindle fibres get attached to the chromosomes at the centromeres.  

Metaphase

During this phase, the spindle fibres pull the chromosome to the opposite poles. As a result, chromosomes get aligned along with the metaphase plate or equatorial plate, an imaginary line passing located in the centre of the two centrosomes.

The metaphase checkpoint ensures that all the chromosomes are aligned along with the metaphase plate. Only then the cell can enter the anaphase.

Anaphase

During this phase, the chromosomes get pulled towards the opposite poles. The tension in the mitotic spindle causes the sister chromatids to get separated.

Thus, the sister chromatids of the duplicated chromosomes are separated and pulled towards the opposite poles. The lengthening of spindles also causes the cell to elongate. 

At the end of anaphase, duplicated chromosomes have been duplicated. The separated chromatids are present at the opposite poles.

Telophase

It is the last phase in the division of the nucleus. This phase is the opposite of the prophase. A nuclear envelope is formed around the segregated chromosomes.

The mitotic spindles also continue to increase in length during the telophase. They cause much more elongation of the cell.

After the formation of the nuclear envelope, the mitotic apparatus disintegrates, and the centrosomes come closer to the newly formed nuclei. 

At the end of telophase, two nuclei are present within the cell at the opposite poles.

Cytokinesis

It is the process during which the cytoplasm of the cell divides. The mitotic cell cycle is completed by the division of the cytoplasm and the formation of two daughter cells.

Animal and plant cells undergo cytokinesis by different methods.

Cytokinesis in Animal Cells

Animal cells do not have a cell wall. Rather, they are bound by a flexible cell membrane. In this case, cytokinesis takes place by the formation of a cleavage furrow.

A slit-like space called cleavage furrow develops in the centre of the cell. It is formed at the same point as the equatorial plate during the metaphase of mitosis. The furrow grows inwards by the inward pinching of the cell membrane. Finally, the furrow from the two ends meet in the centre and the cell gets divided into two equal halves.

Cytokinesis in Plant Cells

Recall that plant cells have a thick wall around the flexible plasma membrane. Thus, they cannot undergo division by the formation of a cleavage furrow as seen in animal cells.

In this case, the Golgi apparatus makes special vesicles that will contribute to the cell walls of the daughter cells. These vesicles align in the centre of the cell at the same point as the metaphase plate was formed. As a result, a cell plate is formed in the centre of the cell, dividing it into two equal halves.

Finally, the cell wall forms along the cell plate and the cell gets divided into two daughter cells.

Summary

• Mitotic cell cycle is a series of stages that finally results in the formation of two daughter cells from one parent cell.
• G1 phase is the initial growth phase during which cell increase in size, makes mRNA, and starts protein synthesis.
• Increase in size is due to synthesis of new organelles.
• The mRNA molecules made are necessary for protein synthesis.
• Proteins made in this process are necessary for DNA duplication in the next phase.
• Some cells fail to follow the normal cycle and enter the silent G0 phase. The G0 phase may be reversible or irreversible. Some cells enter the G0 phase due to environmental factors while others do so as a developmental process.
• During the S phase, DNA of the cell is duplicated.
• DNA replication begins at specific origin sites and is carried out by DNA polymerase enzyme.
• New histone proteins are also synthesized during S phase and nucleosomes are also replicated. The replicated nucleosomes contain all newly synthesized histones.
• Different checkpoints ensure that the DNA replication has been completed without any error.
• In the second growth phase (G2), cell further increases in size and makes proteins. These proteins are necessary for the mitosis ahead.
• The M phase or mitosis includes division of nucleus as well as cytoplasm.
• The division of nucleus takes place in four steps.
• The nuclear envelope disappears, mitotic spindles are formed, and chromosomes become visible during prophase.
• During metaphase, chromosomes are aligned along the equator of the cell.
• During anaphase, chromosomes separate as the sister chromatids get pulled to the opposite poles.
• The nuclear envelope forms again and two nuclei appear in the cell at the end of telophase.
• Cytokinesis in animal cells occur by the formation of cleavage furrow while in plant cells, it occurs by the formation of cell plate.

Read more about Cell Division – Mitosis and Meiosis

Frequently Asked Questions

What is the difference between cell cycle and mitotic cycle?

Cell cycle represents the overall life cycle of a cell that starts from the moment a cell is formed to the time a cell divides into daughter cells. It includes cell growth, replication of DNA and division of the cell into daughter cells. On the other hand, the mitotic cycle only involves the division of a cell into daughter cells after the DNA has been replicated.

What are the 4 stages of cell cycle?

The 4 stages of the cell cycle include the G1 phase which involves an increase in the size of the cell, the S phase during which DNA replicates, the G2 phase when a cell prepares itself for division, and finally M phase during which a cell divides into daughter cells.

What happens during mitosis?

Mitosis or M phase is the last step of the cell cycle during which a cell duplicates into two identical daughter cells. All the contents of the cell duplicate and are divided equally among two daughter cells. 

What are the 4 stages of mitosis?

Mitosis is carried out in 4 stages that include prophase, metaphase, anaphase and telophase.

References

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