A Eukaryotic Cell Cycle- An Overview

In 1951, Alma Howard (a radiobiologist) and Stephen Pelc (a physicist), conducted experiments with radioactive DNA labelling in plants and gave an outline of the cell cycle that we study today. Initially they conducted the experiment on a mouse but due to its inefficiency they used Broad bean instead. Their research introduced the G1, S, G2, M and G0 Phases.

So, what exactly is the Cell Cycle? It is the series of events occurring in the living cells. It is a strictly regulated phenomenon that involves duplication and division of cellular material between two daughter cells. In multicellular eukaryotes, the purpose of cell cycle is to replace the damaged or dead cells with the new ones.

When studying the cell cycle, the word regulation gets used and emphasized on a lot. The reason for this is that even the smallest mistake in the cell cycle could lead to severe consequences. The most common being cancer because if the cell cycle is not regulated strictly, formation of tumor occurs.

Cellular material includes both the nucleus and the cellular organelles present inside a fully grown cell. Most importantly, the genetic material present inside the nucleus i.e. DNA. It is because of the synthesis and division of this DNA that the cell cycle is very strictly regulated as it is the core basis of all the functioning of any organism. In this article the basics of the eukaryotic cell cycle will be discussed.

Two major events occur in the cell cycle, synthesis of DNA (duplication of the already existing DNA or parental DNA) and equal division of the synthesized DNA into two daughter cells. These are categorized as phases. Namely, the Interphase (for preparation and synthesis) and M phase (for mitosis or meiosis). Mitosis occurs in somatic cells whereas the Meiosis occurs in gametic cells. The time taken for typical mammalian cell to complete the cell cycle is 16 hours. Everything mentioned below will be with regards to a mammalian cell.

1.     Interphase (15 hours)

The cells spend most of its cell cycle time in the interphase. Interphase (a.k.a. the preparatory phase for division) is the phase that eventually leads to the doubling of genome (DNA). Based on the different activities occurring in the interphase, it is further divided into three major phases: –

1. G1 Phase – Gap 1
2. S Phase – Synthesis
3. G2 Phase – Gap 2

All of these together prepare and double the genome.

1) G1 Phase (5 hours)

The sole purpose of a gap phase is to provide the cell with time to make the necessary preparations for DNA synthesis or replication. We all know that DNA replication is a complex process which requires range of proteins and enzymes. As the protein synthesis occur actively in G1 phase, the DNA is present in the form of chromatin (thread like structure). The cell remain busy in carrying out following cellular activities-:

• Synthesis of RNA – the cell needs rRNA, t-RNA and m-RNA for carrying out the protein synthesis (Transcription and Translation).
• Synthesis of Enzymes- (like DNA polymerase, ligase, helicase, topoisomerase, Single stranded binding proteins etc).
• Synthesis of additional ATP – (Energy is required for biochemical and molecular pathways like Transcription, Translation, Replication, Glycolysis etc).
• Cell also synthesizes the raw materials like nucleotide (ATP, CTP, GTC and TTP) made up from pentose sugar, phosphorous and nitrogen base. The nucleotide is the repeating unit of DNA, polynucleotide strand.

As a result of such mass synthesis of biomolecules, the cell grows in size.

At the end of the G1 phase, the cell completely commits itself through a commitment point known as the Restriction Point. After this, no matter what, the cell is due to complete its cycle.

2)  S Phase (7 hours)

The sole purpose of this phase is the synthesis of DNA. It includes:

• DNA Replication – It is divided into three stages namely Initiation, Elongation and Termination. The replicated DNA are called as sister chromatids, they are identical copy of each other.  

• Centriole division in mammals – A centromere is an amorphous structure which consist of two centrioles. The parental cell also inherits centromere to its daughter cells and hence centromere also need to be duplicated. The new centromere is synthesized by the duplication of existing centriole. Each daughter cell receives one centromere i.e. two centriole. The centromere duplication is initiated in G1 phase and concludes in G2 phase called as centrosome cycle. The centrosome is also called as microtubule organizing center. The role of centrosome is to form the mitotic spindle. The mitotic spindle set the stage for the equal division of duplicated DNA using the microtubule. If the centriole cycle is not regulated, it leads to anueploidy condition (unequal distribution of DNA).

• Synthesis of Histone Proteins – Histone proteins (H1, H2, H3 and H4 ) are involved in condensation or supercoiling of DNA. They are rich in positive amino acids; allowing them to interact with negatively charged DNA via electrostatic bonds. For the separation and division of duplicated DNA, the DNA needs to be in supercoiled structure. If DNA is not supercoiled, it may get tangled and become difficult for its equal division.

3) G2 Phase (3 hours)

It is the second Gap Phase called as G2 phase. This period is used by the cell to prepare itself for M phase (Mitosis in somatic & Meiosis in gametic cells). it mainly includes biochemical events and synthesis of various materials required for separation of duplicated DNA in the upcoming M Phase. The following cellular activities occur in the G2 phase –

• Synthesis of protein (for Plasma Membrane formation).
• Synthesis of Tubulin protein (for Spindle formation from centromere).
• Synthesis of additional ATP required for the  movement of chromosomes from equator to pole).
• Synthesis of RNA required for protein synthesis.
• Doubling of all organelles.

The G2 Phase marks the end of the Interphase of the Cell Cycle.

There is also a 4^th phase of the cell cycle which doesn’t always exist. It’ll only be present under certain conditions. This phase is known as the G0 Phase.

4) G₀ Phase (Hours, Days, Weeks, Years)

The G₀ Phase is also known as the Quiescent Phase or Resting Phase. In this phase, the cell doesn’t undergo any processes related to cell division. The cell enters this phase under unfavorable conditions and could stay in the same for hours, days, weeks and years. Once favorable conditions prevail, the cell will go back into the cell cycle. For example, Lymphocytes in human blood are in the G₀ Phase. However, upon interaction with an antigen, they re-enter the cell cycle.

Although, some cells never go back into the cell cycle and exist in the G0 Phase permanently until they die. These include Kidney cells, Heart cells, Liver cells, Neurons, etc.

2. M Phase (1 hour)

The M Phase is the phase of division of the already duplicated DNA. This too is a very accurate procedure and requires utmost fidelity. It is divided into two:

i) Karyokinesis (Nuclear division)

Karyokinesis is the division of the Nucleus into two. It includes 4 other sub-phases.

• Prophase – Chromosome is condensed using histone proteins, nucleolus dissolves, Nuclear membrane is broken down
• Metaphase – the duplicated or sister chromatids gets aligned in the middle of the mitotic spindle
• Anaphase – The sister chromatids tend to separate and try to move towards the opposite poles.
• Telophase –  The sister chromatids get separate from each other and reach to the opposite poles of spindle apparatus.

ii) Cytokinesis (Cytoplasmic division)

Cytokinesis is the division of the cytoplasm into two which basically means the division of the cell into two daughter cells.

This marks the end of the cell cycle. Once again, the cycle will be initiated upon presence of favorable conditions and extracellular signals.

The time required for cell cycle varies from species to species and from cell to cell type. The following table shared the cell cycle duration for few types of cells.

References –

https://en.wikipedia.org/wiki/Centrosome_cycle

https://sciencing.com/difference-between-centriole-centrosome-13002.html

https://sciencing.com/description-purpose-mitosis-9556.html Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2017). Campbell Biology (11th ed.). Pearson