Cell Cycle

Cell cycle

CELL CYCLE

Phases of cell phases- a somatic cell exist in two main states : a long undividing stage called interphase and a short dividing state termed mitotic or M phase.

      I.            Interphase:- in the interphase, the cell grows by synthesizing biological molecules such as carbohydrates, lipids, protein and nucleic acids. Also the cellular molecules needed for cell decision are stocked. The interphase lasts for 10 – 30 hours. It is further decided into three periods : first gap or G₁ phase, synthetic or S phase, and second gap or G₂ phase. The duration of these phases varies in different organisms.

1.   G₁ phase: this phase represents the gap between previous mitosis and beginning or DNA synthesis. It is a stage of initial growth of a newly formed cell. The cell carries on normal metabolism in preparation for DNA replication. Carbohydrates, lipids, protein (including some non-histons) and RNAs are synthesized in this phase. No change occurs in the DNA content of the cell. The duration of G₁ phase is most variable. It may last from hours to months or years. Many undividing cells, such as muscle cells, nerve cells and fibroblasts, suspend cell cycle after mitosis just prior to S phase. Such cells are said to be in G₀ phase to distinguish them from G₁ cells which will soon enter S phase. The muscles and nerve cells remain in the G₀ phase for the life of the animal and never decide again. However, the fibroblasts that help in healing of wounds grow and divide on demand.

2.   S phase:  it is a phase of duplication of each chromosome by replication of a new DNA molecule on the template of the existing DNA. Each chromosome now consists of two identical sister chromotids held together at the region of primary constriction’s kinetochores, and carries a duplicate set of genes. A diploid cell (2n) thus, becomes tetraploid (4n) at the end of S phase. Synthesis of histone proteins and their mRNAs, and formation of new nucleosomes also occur only in the S phase. On completion of replication, the histone mRNAs are selectively destroyed. Some non-histone proteins are also formed in S phase. By the time the S phase in complete, the duplicated chromosomes have a full complement of histone and nonhistone proteins. Each chromosome has one old and one new DNA chain, and also has old and histones in about equal quantities. The S phase in most eukaryotes lasts for 6 to 8 hours.

Once the S phase begins, G₂ and mitosis follow without delay.

3.   G₂ phase: this phase marks the gap between DNA synthesis and nuclear division. It is a stage of further growth of the cell and preparation for its division. During this phase, RNA transcription and protein synthesis continue. The cytoplasmic organelles such as centrioles, mitochondria, and golgi apparatus, are doubled, protein for spindle and asters are synthesized and active metabolism stores energy for the next mitosis. The G₂ phase in most cells lasts for 2 to 5 hours. Repair of damaged DNA sequences also takes place in the interphase.

A resting cell.  An interphase cell is sometimes described as a ‘’resting cell’’. This is incorrect, as the cell does not rest even when it is not dividing. Thought it does not show the changes on the above vital activities. In fact, interphases are the most active period of the cell. Some workers have suggested the term energy phase for it.

   II.            Mitotic phase: - mitotic or M phase follows the interphase. It is aimed at orderly distribution of the already duplicated chromosomes to the daughter cells. The latte is diploid, and contains exactly the same hereditary information as the parent cell. Other cell components (organelles and molecules) are divided approximately equally between the daughter cells, although not wish the same precision as the DNA. After the completion of mitosis, the daughter cells enter the G₁ phase of the next cell cycle.

Many structural and physiological changes occur in the cell during mitosis. Chromatin of the nucleus is packed into visible chromosomes, which are set free by breakdown of nuclear envelope. There is an extensive reorganization of the membranous components and cytoskeletal elements. Endoplasmic reticulum and golgi apparatus breakdown into small vesicles. This stops protein movement. Microtubules dissociate into tubulin dimmers, which are assembled into the spindle. The latter occupies most of the cell and assists in the distribution of chromosomes into the daughter cells. Actinfilaments are recognized to form a contractile ring for the cytoplasmic division.

As a result of the above changes, the former activities of the cell, namely, gene expression, protein synthesis, secretion and cell motility stop. Cell’s entire attention is devoted to the process of division.

The purpose of these changes is to decide the components of the parent cell equally between the two daughter cells. The mode of distribution depends on the nature of the components. The organelles which occur in many copies are divided by their sheer distribution in the cytoplasm. Approximately half of the cytoplasm is received by each daughter cell. The single nucleus breaks down so that two nuclei are reconstructed from its components. The breakdown of sheet-like ER into vesicles allows the reformation of ER in the daughter cells from the vesicles that pass into them during division.

Definition of cell cycle – the regular sequences of G₁, S, G2 and M phase phases is called the cell cycle.

Duration of cell cycle: under optimum conditions of nutrition’s and temperature, the duration of cell cycle for a particular kind of cell is constant. Under less favorable conditions it may become longer, but it is not possible to speed up the cell cycle and make cells grow faster. This shows that the duration of cell cycle is the time required for carrying out some precise programmer that has been built into each cell. This programmer seems to include replication of chromosome and doubling of all other constituents of the cell meant for growth.The interphase between the two meiotic divisions in unique in lacking a DNA synthesizing S phase.

Variation in cell cycle phases: cell cycle of mammalian cells in culture takes 10-30 hours. In an adult human cell, G₁ lasts for 8 hours, DNA is synthesized for 6 hours in S phase, G₂ Continues for 4-5- hours, and mitosis is completed within 1 hour. The maximum variation on the cell of similar cells affects the duration of G₁. The duration of S and G₂ shows the least variation in response to external conditions.

Cell cycle of most growing animal and plants cells takes 10-30 hours. M phase lasts for more than 1 hour in plant cells.

Embryonic cells show a lot of variation in their cell cycle. Cells of many animal embryos undergo rapid divisions, forming progressively small cells. The rate of DNA synthesis is about 100 times faster in these non growing embryonic cells than it is in the adult cells of the same species. These are usually no G₁ phase, and DNA synthesis starts during or immediately after the M phase. The embryonic cells of Xenopus (a toad) have 25 minutes cell cycle. There is no G1 phase. S phase lasts for less than 15 minutes and starts during telophase of mitosis, G₂ is 20

Many protozoans, fungi and other lower organisms have a relatively brief cell cycle devoid of G₁ phase. The G₁ phase appears to be correlated with the amount of growth and biosynthesis taking place in the cell. If growth is minimum, as in animal embryos, or very rapid, as in lower organisms grown under optimum conditions, the G₁ phase is short or lacking. The G₁ phase can be easily done away with because S phase may begin before M phase is completed. The S and M phases are essential and usually there Is G₂ phase in between.

Mitosis occurs after DNA synthesis has taken place. If DNA synthesis stops, the cell does not undergo mitosis. The cell also does not divide if protein synthesis is stopped during G₂ phase. Both structural and enzymatic proteins are needed by the cell to undergo mitosis.

The cell cycle is prokaryotes consist of DNA replication followed immediately by cell division. Escherichia coli can divide in 30 minutes and only a minute or so of this time is used in DNA replication.

Potential of cells for growth and division: The cells of an organism vary in their capacity to grow and divide. Three categories of cells are recognized regarding their potential for growth and division –

                              i.            Permanently or terminally differentiated cells: these cells undergo extreme structure specialization and lose their ability to divide forever. Examples: muscle cells, nerve cells, red blood corpuscles.

                           ii.            Temporarily differentiated (quiescent) cells: These cells are differentiated and normally do not divide. However, they can be induced to begin DNA synthesis and divide by appropriate stimuli. E.g. liver cells can be induced to start proliferation by surgical removal of a part of liver. Lymphocytes can be induced to divide by interaction with suitable antigen. Fibroblasts are stimulated to proliferation on injury to a tissue for healing.

                        iii.            Undifferentiated cells: these cells retain the ability to divide. Their descendants replace the lost cells in certain tissues, such as epithelia and blood, under normal physiological conditions. These reserve cells are often called stem cells.

The quiescent cells usually have duplicated DNA and are said to be in G₀ state. Some epithelial cells may rest in G₂ phase.

Control of cell cycle: the mechanism that controls the cell cycle is at present the subject of an intensive research in cell biology. This mechanism can reveal the ways in which cells work, and more importantly why cells grow and divide in an uncontrollable manner in cancer.

As the beginning of the S phase eventually leads to cell division, it is important to find out what triggers DNA replication. Many views have been expressed:-

                     i.            Nucleo-cytoplasmic ratio: Hertwig in 1910 proposed that cell division starts when the ratio between the volume of the nucleus and the volume of the cytoplasm is upset. Growth of a cell involves the synthesis of protein, nucleic acids, lipids and other cellular components. The synthesis requires the movements of materials back and forth through the nuclear and cell membranes. As a cell grows, its volume increases more than the surface of the nucleus and the cell. At a critical point, the surface of the nucleus becomes inadequate for the exchange of materials between the nucleus and the cytoplasm required for further growth. At this stage the cell divides and regains the nucleocytoplasmic ratio that allows growth.Although cell division usually takes place after a cell has grown to a certain size, there are important exceptions to this pattern. During embryonic development of many animals, cell divisions occur without a net increase in the size of the embryo. The eggs of many animals grow very large before division.

                  ii.            Surface-volume ratio: usually it is held that the surface-volume ratio of a cell plays an important role. As a cell grows in size, its volume increases more than its surface. Since a cell draws all materials for maintenance and growth through its surface, a stage will reach when the surface area is insufficient to supply the large volume. It has been suggested that these is a critical point in the surface-volume ratio at which the division starts. The division   of the cell greatly increases the surface without increasing the volume.

This theory too fails in some cases. If the cells are started, they may divide without doubling their size and smaller daughter cells.

               iii.            Nucleolus: nucleolus has also been assigned a trigger function because damage to it at a certain critical time (telophase to midprophase) stops cell division.

                iv.            Cyclic nucleotide: it has been  found that two cyclic nucleotides, cAMP , and cGMP , influence cell division. Concentrations of these nucleotides vary regularly during cell cycle. In many cells, the concentration of cAMP is high during G₁ phase, significantly drops as the cells enter S phase and mitosis, and rises again in the next G₁ phase. The concentration of cGMP often varies in the reverse pattern. It is low in G₁ phase , becomes high in the beginning of S phase and fails again by the end of M phase. Addition or removal of either of these nucleotides can start of stop entry of many cells into S phase and the subsequent M phase.

                   v.            In many cells, the concentration of these cyclic                   nucleotides remains constant throughout cell cycle. Plant cells do not have cycle nucleotides. In view of these facts, cyclic AMP and GMP are no longer through to regulate cell cycle.

                vi.            Phosphorylation: the number of phosphate groups added to the histone group, particularly to H1, varies during the cell cycle. Typically phosphate groups are added to H1 as the cells enter S phase, increase during M phase, and are removed on the completion of mitosis before G₁ starts. Addition and removal of phosphate groups to the nonhistone proteins have also been noted during the cell cycle. These changes in the histone and nonhistone proteins occur in organisms as diverse as fungi, plants and animal. It seems likely that changes in the histones and nonhistones may have a role in the control of cell cycle because these proteins have been found to regulate the activity of genes of genes in RNA transcription during interphase.

                         vii.            Cyclin: mitosis appears to be controlled by the concentration of a protein builds up in the cell during interphase and is degraded during mitosis. Uncontrolled mitosis leads to cancer. Certain radiations, smoking, toxic chemicals, some viruses,etc., cause cancer.