Essay on the Cell Cycle

The below mentioned article provides an essay on the Cell Cycle.

Rudolf Virchow (1855, 1859) was the first to suggest that new cells are formed from the division of the pre-existing cells— omnis cellula e cellula (every cell is derived from a cell). In 1873, Strasburger similarly proposed that nuclei are formed from pre-existing ones.

Boveri (1879) and Flemming (1879, 1880) studied details of somatic cell division. Flemming (1882) coined the term of mitosis for it. Van Benedin (1887), Strasburger (1888), Sutton (1900) and Winiwater (1900) studied the details of division that occur prior to the formation of gametes.

They found that chromosome number is reduced to half in gametes as compared to their parent cells. The division was termed as meiosis by Farmer and Moore (1905).

Cell cycle is a genetically controlled series of changes that occur in a newly formed cell by which it duplicates its genome, synthesizes other constitu­ents, undergoes growth and divides to form two daughter cells. All these events occur in a coordinated manner and are under genetic control.

Various phases of cell cycle are controlled by proteins cyclins and cyclin dependent protein kinases (CDKs). Protein kinases are enzymes that phosphorylate proteins using ATP. It leads to breakdown of nuclear membrane. The transition from G₁ to S and from G₂ to M is carried by these CDKs.

Actually there are two regulatory mechanisms, called check points which take decision about cell division (Fig. 10.2). First check point, called G₁ cyclin (C_G1 or G₁/S) lies in between G₁and S. In G₁, CDK becomes active by G₁ Cyclin and ATP at its activation site.

It causes transition of G₁ to S phase. G₁ cyclin is destroyed at the end of S phase and CDK becomes inactive. Cell enters G₂. Second check point lies between G₂ and M. In G₂, inactive CDK binds to second check point, mitotic cyclin (C_M or G₂/M).

It gets phosphorylated at its both activation and inhibitory sites but still remains inactive. On removal of PO₄ from the inhibitory site, it gets active and cause transition from G₂ to M phase. At the end of M phase, cyclin C_M is degraded and PO₄ at activation site is removed and the cell enters G₁ again.

In embryo, meristems and other generative regions, the cells undergo repeated divisions. The time interval between two cell cycles is called generation time. Generation time varies from a few minutes to a few days depending upon the type of cell and its environmental conditions.

In culture, human cells divide once every 24 hours (10 hrs. in G₁, 9 hrs. in S, 4hrs in G₂ and 1 hr. in M phase). It is 90 minutes in case of yeast and 20 minutes in case of bacteria.

Cell cycle consists of two basic phases, states or periods. There is a long non-dividing growing I-phase and a short-dividing M-phase. Both have sub stages. M-phase is the period or basic phase of actual cell division. It is of short duration as compared to I-phase. In the average duration of 24 hours in the cell cycle of dividing human cell, M-phase lasts for a mere one hour (less than 5% of total). I-phase represents interphase.

I. Interphase:

Interphase (L. inter- between, Gk. phasis-aspect) is a series of changes that take place in a newly formed cell and its nucleus before it becomes capable of division again.

Therefore, it is also called intermitosis. Previously it was called resting stage because there is no apparent activity related to cell division. The interphase cell is metabolically quite active. There is rep­lication of various subcellular com­ponents including chromosomes.

Cell grows in size and becomes al­most double. At the end of inter­phase the cell becomes ready for equitable division into two equal daughter cells. Some workers term interphase as energy phase. Inter­phase occupies 75-95% of the total generation time.

However, the non-dividing state of the mature cell and its nucleus is also called interphase. It lasts throughout the life of the cell. Human nerve cells do not divide after birth. Therefore, interphase period of human nerve cells, lasts throughout the life of a person. Interphase of a dividing cell has three stages— G₁, S and G₂.

1. G₁-Phase (First growth phase or Post mitotic Gap phase):

It is phase between end of M-phase of previous cell cycle and initiation of DNA replication. G₁ is the longest phase of interphase. The cell is metabolically active and grows continuously.

Nucleus, however, grows only to a small extent. RNA and proteins are synthesised. A large number of nucle­otides, amino acids for histone synthesis and energy rich compounds are formed. Cell organelles also increase in number. Duration of G₁ phase is variable. It is longer for cells dividing infrequently.

A shorter G_1-phase occurs in cells undergoing frequent divisions. In G₁-phase, a cell has three options,

(i) To continue cell cycle and enter S-phase.

(ii) Stop cell cycle and enter G₀ phase for undergoing differentiation,

(iii) Get arrested in G_1-phase whence it may enter G₀ phase or re-enter cell cycle.

The deciding factor is availability of mitogens and storage of energy rich compounds at the deciding point called check point. This check point is called G, cyclin or C_G1. It causes transition of G₁ to S phase. Once the check point of G_1-phase is crossed, cell cycle will go on uninterrupted till it is completed.

2. S-Phase. In S-phase (synthetic phase) the chromosomes replicate:

For this their DNA molecules function as templates and form carbon copies. The DNA content doubles i.e., 1C to 2C for haploid cells and 2C to 4C for diploid cells. As a result duplicate sets of genes are formed. Along with replication of DNAs, new chromatin fibres are formed which, however, remain attached in pairs and the number of chromosomes does not increase i.e., In to In and 2n to 2n.

As chromatin fibres are elongated chromosomes, each chromosome comes to have two chromatin threads or sister chromatids which remain attached at a common point called centromere.

S-phase is also called invisible phase of M-stage since it is in this phase that the chromosomes prepare themselves for equitable distribution later on. Subunits of kinetochores are synthesised. Centrosome also begins to divide in centriole containing cells to form two centrosomes or centriole pairs.

3. G₂-Phase:

In G₂-phase (second growth phase or pre-mitotic gap phase) synthesis of DNA stops. However, formation of RNAs and proteins continues. They are required for multiplication of cell organelles, spindle formation and cell growth. It prepares the cell to undergo division. The second check point called mitotic cyclin (C_M) lies between G₂ and M phase and causes transition from G₂ to M phase.

II. Mitotic Phase (M-phase):

M-phase is the final phase of cell cycle. It represents the phase of actual division. Prior to it, the cell components have undergone duplication. M-phase is, therefore, the stage of separation of already duplicated components. It consists of karyokinesis (division of nucleus) and cytokinesis (division of cell protoplast).

After M- phase a cell may re-enter fresh cycle or pass into G₀-phase. G₀-phase (Lajtha, 1963) is the stage when cell cycle is arrested. Therefore, further divisions stop. The cell may then grow in size and become differentiated.

G₀-Phase (Quiescent Stage):

It is the stage of inactivation of cell cycle due to non-availability of mitogens and energy rich compounds. The cells remain metabolically active. They do not grow or differentiate.

The cells function as reserve cells which can join cell cycle any time. Differentiation Phase. Most of the cells leave the G₁-phase midway. They grow in size, assume particular shape and come to have a particular function. The phenomenon is called cell differentiation.