Click4Biology: Cell division

2.5.1 Stages of the cell cycle

The cell cycle described the major phases of activity between cell division of a cell. The length of the cell cycle depends on the particular cell. For example bacterial cells can divide every 30 minutes under suitable conditions, skin cells divide about every 12 hours on average, liver cells every 2 years, and muscle cells never divide at all after maturing, so remain in the growth phase for decades.

• The total length of a cell cycle varies depending on the specialised function of a cell.

• Interphase (gray) is the longest phase which itself occurs in three stages.

• G1 The cell performs its normal differentiated function. Protein synthesis/ mitochondria replication/ chloroplast replication.

• S DNA replication. At this point the mass of DNA in the cell has doubled.

• G2 Preparation for cell division

• Phases of mitosis (see 2.5.4)

• Cytokinesis: division of the cytoplasm to form two daughter cells.

 

2.5.2 Tumours

'Tumours are not foreign invaders. They arise from the same material used by the body to construct its own tissues. Tumours use the same components -human cells- to form the jumbled masses that disrupt biological order and function and, if left unchecked, to bring the whole complex, life sustaining edifice that is the human body crashing down'.

R. Weinberg, R. (1998) One Renegade Cell. London:Phoenix, Science Masters Series.

 

• Tumours (cancers) are a cell mass formed as a result of uncontrolled cell division.

• They can occur in any tissue.

• Stomach cancer

 

 

Cells are normally in state of repressed mitosis. The default condition is for the cell to progress into mitosis and cytokinesis. In a tumour something happens (mutation to the proto-oncogene) to release the repression of cell division. The cell begins to divide in an uncontrollably manner. The mutation of the proto-oncogene into the oncogene and the expression of that oncogene results in the loss of control of cell division.

Evolution of Cancer:

1. Multi step carcinogenisis: Cancers do not arise as invasive malignant metastatic (spreading) tumours. Rather they follow a series of steps that begins with a contained benign growth. A cell will eventually arise within the benign mass which is more aggressive in its growth rate and with a tendency to invade surrounding tissue. These cells have a selective advantage and will become the dominant cell type within the tumour. The cancer has now progresses to an aggressive invasive form. In the next stage a further mutation to a cell makes this cell not only aggressive and invasive but with a tendency to break up and spread to other tissues (metastasis). This latter tumour stage is the malignant tumour

2. Oncogene activation: There are within a cell many proteins that are either cell signals or control proteins within the cell cycle. The proteins are coded for by genes and are referred to as proto-oncogenes. When transformed by mutagenic agents( chemicals, radiation) they are transformed (mutated) into oncogenes. It is these oncogenes that when expressed will cause a loss of control of division within that cell. There is then the production of a protein that signals the cell internally to increase the rate of cell division. Since this gives these cells a selective advantage they become more common at the expense of non-mutated cells. These types of genes that create transform cell function were discovered as early as 1910.

3. Tumour Suppressor deactivation. An alternative or additional feature is the idea of tumour suppression which holds cell division in check. The tumour suppressor could simply be a protein that inhibits the cell cycle. Alternatively there are proteins that repair DNA which also suppress tumour suppression by maintaining the integrity of DNA. Therefore the suppression is removed and the cell progresses into uncontrolled cell division.

The suggestion form this description therefore is that the development of a cancer will require atleast two mutations; one of the proto-oncogene; two of the tumour suppressor.

Cancer exerts its deleterious effect on the body by: destroying the surrounding adjacent tissues: e.g. compressing nerves, eroding blood vessels, or causing perforation of organs: replacing normal functioning cells in distant sites: e.g. replacing blood forming cells in the bone marrow, replacing bones leading to increased calcium levels in the blood, or in the heart muscles so that the heart fails.

 

2.5.3 Interphase

• The cell specialises to a particular function in a process called differentiation.

• Through protein synthesis and gene expression there is a specialisation of cell structure and function.

• During this interphase the cell carries out this specialist function.

• The length of the interphase varies from one type of cell to another.

• G1 follows cytokinesis. The cell is involved in the synthesis of various proteins which allow the cell to specialise.

• S phase involves the replication of DNA molecules which takes place prior to the phases of mitosis.

• G2 preparation for the phases of mitosis which involves the replication of mitochondria and in the case of plants, the chloroplast.

 

2.5.4 Stages of mitosis

Super coiling: Eukaryotic DNA is combined with histone proteins and non-histone proteins t o form the readily stainable chromatin. The method of folding of chromatin is specific to each chromosome leaving genes in predictable positions and a distinctive overall chromosome shape. The human cell has a DNA length of about 1.8 m this has to be packed into a nucleus which has only a 5 um diameter. This packaging process requires up to a X 15,000 reduction. This super coiling makes the structure so dense that it can be see with a light microscope during the phases of mitosis.

a)The cell membrane is intact during this the interphase. G1,S and G2 cannot be seen with a light microscope.

b) G1,Within the nucleus, genes on the chromosome are being expressed to carry out normal cell function (interphase)

c) S-phase in which DNA replication occurs and the chromosomes are copied. The copies called sister chromatids are held together by a centromere.

d) Early Prophase in which the sister chromatids have condensed by super coiling. Note the formation of the spindle microtubules and their attachment to centrioles. The nuclear membrane will now break down to reveal sister chromatids

e) Metaphase the chromosomes arranged on the equator of the cell each attached to a spindle microtubule at the centromere

f) Anaphase: The spindle microtubules contract and pull apart the sister chromatids one to each pole of the cell. The centromere splits allowing the sister chromatids to be separate.

g) Telophase: at each pole there are separate groups of the replicated chromosomes the spindles is degenerating

 

h) Cytokinesis: the cell membrane begins to separate, dividing the cell into two new cells. The nuclear membrane is reforming

i) Two daughter cells are formed. They are genetically identical to each other and in effect the basis of a clone. (see 2.5.6)

 

2.5.5 Nuclei of daughter cells

• The process of cell division produces genetically identical daughter cells.

• Conservation of chromosome number. The chromosome number in each of the daughter cells is the same as that of the original cell

• During the S-phase, each chromosome is copied exact. The two copies of each chromosome are held together by a protein structure called a centromere.

• Therefore just prior to the phases of mitosis there is actually double the number of chromosomes present in a cell.

• Each chromosome in this state is represented by a pair of sister chromatids. These give the now classic cross image of the DNA (see image below)

 

This pair of sister chromatids image was taken during one of the phases of mitosis.

The two sister chromatids are held together at the centromere

The arms of the chromatids are visible because of a condensation of the molecule called super coiling.

This condenses the molecule some x 15,000 times of its original length The pairs of sister chromatids is a non-random organisation. The position of genes is predicable within the structure seen here. Also there is a unique shape to each of the chromosomes.

 

 

Purposes of Mitosis

 

• Growth: multicellular organisms increase their size through growth. This growth involves increasing the number of cells through mitosis. These cells will differentiate and specialise their function.

• Tissue Repair: As tissues are damaged they can recover through replacing damaged or dead cells. This is easily observed in a skin wound. More complex organ regeneration can occur in some species of amphibian.

• Asexual Reproduction: This the production of offspring from a single parent using mitosis. The offspring are therefore genetically identical to each other and to their “parent”- in other words they are clones. Asexual reproduction is very common in nature, and in addition we humans have developed some new, artificial methods.