Interphase

 

 INTRODUCTION :

All multicellular organisms start life as a single cell, the fertilized egg or zygote, and grow by addition of new cells. The new cells arise by division of the preexisting cells. This fact was first suggested by Rudolf Virchow in 1858 in the aphorism ¹ " Omnis cellula e cellular", meaning " every cell from a cell". Thus, the continuity  of life depends on the cell reproduction, or cell division. Strasburger,in 1873, suggested that the nuclei also are formed from the preexisting nuclei. Boveri ( 1879) and Flemming ( 1879,1880) provided details of somatic cell division and Flemming  ( 1882) later used the term mitosis for such a division. Similarly,  term meiosis was coined by Farmer and Moore ( 1905)  for reductional division that occurs prior to the formation  of gametes.

Walther Flemming ( 1882): Flemming is often credited with first accurately describing the process of mitosis in animal cells. He identified the division of the nucleus into two daughter nuclei and the subsequent separation of the cytoplasm, and he discovered and named structures known as chromosomes.

Walther Flemming (1843-1905) was a German biologist and histologist who made significant contributions to our understanding of cell division and chromosome behavior. He is often credited with being one of the founders of modern cytology.

Flemming's most famous work was his detailed observations of cell division, specifically in animal cells. In the late 1870s and early 1880s, he conducted extensive studies on the process of mitosis (cell division) and described it in great detail. He observed the division of the nucleus into two daughter nuclei and the subsequent division of the cytoplasm. Flemming also discovered and named the structures known as chromosomes, referring to their ability to take up different staining dyes.

In addition to his work on mitosis, Flemming also investigated other aspects of cell biology. He conducted research on various tissues and cells, studying their structure and functions. Flemming is also known for his studies on cell membranes and cell movements.

Flemming's research laid the foundation for our understanding of cell division and the importance of chromosomes in inheritance. His detailed observations and descriptions of mitosis paved the way for further research in the field and influenced subsequent scientists in the study of cytology and genetics. Today, Flemming is regarded as one of the pioneers of modern cell biology.






   The chromosomes, or DNA, of a  parent cell must be double exactly  if the daughter  cells formed by its division  are to have identical information  about their structure  and functioning. This  duplication  of chromosomes, or DNA, does occur well before cell division begins. Each new cell must inherit  not only a nucleus containing  the entire genetic information  it wi needs, but also the cytoplasmic organelles required  to express the genetic information, such as ribosomes to synthesize proteins and mitochondria to supply the necessary  energy. The mode of cell division  is fundamentally similar  in all organisms. This emphasises the unity of life.

 Theory: 

Rudolf Virchow was the first to suggest  that new cells are formed from the division of the pre_ existing  cells _ omnis  cellular e cellular .Strasburger proposed that nuclei are formed pre_ existing ones.

   A cell division  when it has grown to a certain maximum size, which disturbs the karyoplasmic ratio.Cell  division  is also controlled by mitogens.Mitogen is  a factor that triggers  cell division . The common plant mitogen is cytokinin. There are several  mitrogenic substances known in human beings, e.g. lymphokines, EGF ( epidermal  growth factor), PDGF ( Platelet  derived growth factor), etc. Period between  two successive division is called generation time.The series of changes which involve  the growth  and division of a cell is called cell cycle.

CELL CYCLE:

Cell cycle was described by Howard and Pele in 1953


The sequence of events by which a cell duplicates its genome and synthesizes other cell contents and  eventually divides into two daughter cells is termed as cell cycle.


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


  The cel cycle regulated at certain check points by both internal and external controls. A check point in the cell cycle is a critical control point where stop and go ahead signals can regulate the cycle. Three major  check points are found in the G1, G2 and M_ phases. For many cells, the G1 check point_ doubled the restriction point in mammalian cells seems to be the most important. Three classes of cyclin _ cdk complexes control passage through the cell cycle _ the G1, S_ phase and mitotic Cdk complexes. 

In simple words, the cell cycle refers to the sequence  of events involving  growth and division  of a cell from the time of its formation ( by division of the parent cell) to its own  division  into daughter  cells.

Generation Time:

Duration of the cell cycle,  i.e., period between  two successive cell divisions,  is called generation time.It depends  on the type of cell and external factors such as temperature and food and oxygen supplies. Bacterial cells divide every 20 minutes, epithelial cells of the intestinal lining every 8__10  hours, and onion root __ tip cells may take 20 hours. Mammalian ( e.g., humman) cell divides once in approximate every 24 hours and a yeast cell only in about 90 minutes. 

Phases of Cell Cycle:

Cell cycle consists of two states, a long nondividing growing I_ phase and short dividing  M_ phase, I_ phase represents interphase.Interphase is a series of change 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. Some workers term interphase as energy phase. The nondividing state of the mature cell and its nucleus is also called interphase. Interphase occupies  more than 95% of the total generation time. In mammals nerve cells do not divide at all after birth. Thus, for a human neuron the interphase period lasts the entire lifespan of a person.These main phases are followed by a still shorter phase of cytoplasmic division  known as cytokinesis  or C phase.

        Various  phase of cell cycle are regulated  by proteins cyclins  and cyclin dependent  protein kinases ( CDKs) .The  latter phosphorylate proteins  using ATP resulting  in the breakdown  of nuclear membrane . In fact,  two regulatory mechanisms ( called check points) are carried by these CDKs ; the first check point lies in between  G1 and S  phase and second check point lies between  G1 and M phases. These  check points take decision about cell division. 

 Cell Cycle Stages (Interphase):




Interphase involves  a series of  changes  that  newly formed cell and its nucleus undergo to become fit for division. Interphase is a period of intense synthesis and growth. The cell  produces biological molecules, such as carbohydrates , lipids, proteins and  nucleic  acids, needed for its growth and carrying out its specific functions. Also the cellular molecules needed for cell division are stocked. The interphase lasts for 10_ 20 hours, and takes 75 to 90% of the entire generation  time. It is further divide into three period: first gap¹ or G1 phase, synthetic or S phase, and second gap or G2 phase. Duration of these phases varies  in different  organisms.
 It division into three stages : G1, S and G2.



A diagrammatic  view of different phase of cell cycle

(1):  G_ phase:  

In G1 _ phase ( first growth phase  or post mitotic gap phase ) RNA and proteins  ( histones  are synthesized during S_ phase) are synthesised. The nucleus and cell grow in size. A number of nucleotides, cell organelles, amino  acids for histone synthesis  and energy  rich compounds are formed. In G_ 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_ 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. The regulation of the duration of the cell cycle occurs primarily by arresting it at a specific point of G1_ phase. It is during G1_ phase that a cell must decide whether the cell will start a new cycle or become arrested  in the G0 state. Once this G1 check point has been passed, the cell goes on to complete a  new cycle. 

(2) S_ phase: 

In S_ phase ( synthetic  phase) the chromosomes ( including histones) replicate. The DNA content doubles. With replication of DNAs, new chromatin fibres are formed which, however , remain  attached in pairs.Each chromosome comes to have two chromatin thread or sister chromatids which remain attached at a point called centromere. If the cell had diploid of 2n number of chromosomes at G1, even after S phase the number of chromosomes remains the same, i.e., 2n.thus, becomes tetraploid ( 4n) at the end of S_ phase is also called invisible phase  since it is in this phase  that the chromosomes prepare themselves  for equitable  distribution later on. Subunits  of kinetochores are synthesised.  Histone proteins are also formed in the  associated  with each DNA strand, forming nucleosomes. Some nonhistone proteins are also formed in the S phase. The S phase in most Eukaryotic cells lasts for 6 to 8 hours. Once the S phase begins, the cell must undergo  mitosis.Centrosome also divides in centriole containing cells to form two centrosomes or centriole pairs.


3): G2__ phase:

G2__ phase ( second growth phase or pre__ mitotic gap phase) has double DNA content as compared  to the original cell. The phase produces macromolecules ( RNAs, Proteins) for multiplication of cell organelles, spindle formation  and cell growth.It prepares the cell  to undergo division. The cytoplasmic organelles, such as centrioles mitochondria and Golgi apparatus, are double, membranes  are assembled  and stored  in small vesicles,  proteins for spindle  and asters are synthesized, and active metabolism stores energy for the next division.  The G2 phases in most cells last for 2 to 5 hours. Some proteins  formed  in G2 cause condensation of chromosomes to initiate mitosis.

RNA  synthesis  occurs throughout  interphase and stops during mitosis. A typical Eukaryotic cell cycle is illustrated by human cells in culture. These cells divide once in approximately every 24 hours. Yeast can progress through the cell cycle in only about 90 minutes. In the 24 hour average  duration  of cell cycle of  a human cell, cell division  proper lasts for only about an hour.Generally speaking, the S, G2 and mitotic periods are relatively constant in the cells of the same organism. The G1 period is the most variable  in length. Depending  on the physiological  condition of the cell, it may last days, months or years. 

DNA  Repair: 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. Though it does not show the change characteristic of a dividing cell, its carrying  on the  above vital activities. In fact, interphase  is the most active period of the cell. Some workers have suggested  the term energy phase for it.

Mitotic Phase ( M __ Phase ): 

Mitotic or M phase follows the interphase. Ot starts with the nuclear division, corresponding to the separation of daughter  chromosomes Karyotinesis) and usually ends with the division of cytoplasm ( Cytokinesis). It is aimed at orderly distribution  of the already duplicated  chromosomes among the two daughter nuclei. 

After karyokinesis, mitosis is usually  followed  immediately by an equal division of the cytoplasm, dividing the cell organelles and macromolecules approximately equally between  the daughter cells.Cytokinesis is followed by separation of the two daughter cell. The latter are diploid and contain identical sets of chromosomes,  and hence exactly  the same hereditary information as the parent cell.




Postmitotic Event: After  the completion of mitosis, the daughter  cells may enter the G1 phase of the next cell cycle or G0 phase.

G0 phase:

The cells, which are not to divide further,  do not proceed beyond  the G1 phase and start undergoing  differentiation into specific  types of cells. Such cells are said to be in quiescent  stage or G0 phase of cell cycle to distinguish  them from G1 cells which will soon enter S phase. Cells in G0 phase remain metabolically  active but no longer proliferate unless called on to do so depending on the requirement of the organism. Some of the G0 phase cells, such as fibroblasts,  which help in healing  of wounds, grow and divide again on demand  of the body. Some types of cells do not divide after attaining full differentiation and finally die. These include nerve cell¹, skeletal  muscle cells, mature circulating white blood corpuscles and red blood cells.

   The most important  event in the regulation of cell cycle  occurs  in the G1 phase. A G1 cell commits whether  to restart a new cell cycle  or to enter the G0 phase.

Alternative Definition of  Cell Cycle


The  regular sequence  of G1, S, G2 ( Interphase) , and M ( Mitotic) phase is called the cell cycle 



Duration of  Cell Cycle :

Under optimal conditions of nutrition and temperature,  the duration  of cell cycle for  particular kind of cell is constant.Under less favourable 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 the cell cycle is the time required for carrying out some precise  programme that has been built into each cell. This programme seems to include replication  of chromosomes and doubling of all other constituents of the cell meant for growth.


Cell Cycle Diagram 







































  

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