Chapter 5: The Mitotic Cell Cycle

Mitosis is nuclear division that produces two genetically identical daughter nuclei,
each containing the same number of chromosomes as the parent nucleus.

The Cell Cycle

1. Interphase
First growth (G1) phase : cells make the RNA, enzymes and other proteins
needed for growth. At the end of G1, the cell becomes committed to
dividing or not dividing.
Synthesis (S) phase : replication of DNA.
Second growth (G2) phase : organelles / cell grow and divide and energy
stores are increased. Besides, new DNA is checked and any errors are
usually repaired. There is also a sharp increase in the production of the
protein tubulin needed to make microtubules for the mitotic spindle.
2. Nuclear division process by which the nucleus divides.
Mitosis : results in 2 daughter nuclei having the same number of
chromosomes as the parent nucleus. The nuclei formed are genetically
identical to the parent one.
3. Cell division (cytokinesis)
follows nuclear division, and is the process by which the whole cell
divides.

Structure of Chromosomes
1. Made up of mainly of 3 materials:
proteins (70%), mostly in the form of histones, scaffold proteins and
polymerases.
deoxyribonucleic acid (DNA) (15%)
ribonucleic acid (RNA) (10%)
2. During interphase (after DNA replication has taken place), the chromosome is
a double structure made up of 2 identical structures called sister chromatids
joined together by a narrow region called the centromere (no genes in this
region).
3. To pack into a nucleus which is only 6 m in diameter, the considerable length
of DNA in the 46 chromosomes of an adult human cell (about 1.8 metres) is
highly coiled and wrapped around histones (globular proteins), forming a
complex known as chromatin. The chromatin has a beaded appearance due to
the presence of nucleosomes.
4. Nucleosome (cylindrical in shape) consists of a segment of DNA wound in
sequence around eight histone molecules.
5. Nucleosomes line up like a string of beads which can be further coiled and
supercoiled

Stem Cells
1. Stem cells are undifferentiated, unspecialized cells which mean stem cells can
differentiate into any type of cell present in our body and we have around
200+ cell types in our body and stem cell can give rise to any of them.
2. Stem cells are classified under two categories, embryonic stem cells found in
embryo and adult stem cells - found in many organs. Embryonic stem cells can
be either totipotent or pluripotent and adult stem cells are multipotent.

3. Totipotent totus means whole. So the term is about whole of something.

To understand totipotency let us go to fertilization process. When sperm cell
fertilizes an egg it results in the zygote formation, we all know that. This
zygote will then start dividing and differentiating, giving rise to whole
organism. So this ability of zygote that it can differentiate into any type of cell
(making a complete organism) is called totipotency. That means a zygote is a
cell which is totipotent.
4. Pluripotent pluri means several. Now once the zygote is formed, it will
start dividing and after few divisions it will reach the blastocyst stage. At this
stage it is a hollow ball which has a cluster of cells called inner cell mass and a
single cell line at the periphery called trophoblast. The inner cell mass of the
blastocyst has the ability to produce all the cell types of our body except for
what trophoblast can form e.g., placenta, amniotic sac etc. So this means we
have around 200+ cell types in our body and inner cell mass can differentiated
into any of them, e.g., it can give rise to all the blood cells, cardiac muscles,
neural cells. This ability of inner cell mass is called pluripotency. So inner cell
mass cells are pluripotent and we wouldnt call it totipotent because it cannot
give rise to what trophoblast cells can.

5. Multipotent multi in this case means few. As in the classification we

saw that multipotent is term related to adult stem cells. Adult stem cells are
found in many organs which mean they are already specified to differentiate in
particular cell line, depending on which organ they are present in. To make it
easier to understand let us compare it with pluripotent stem cells. Pluripotent
cells, as we already establish can differentiate in any of the cell type but
multipotent cell would be more specified for one or more cell lines e.g.,
mesenchymal stem cell differentiates to form bone, cartilage, connective
tissue, adipose tissue etc. So mesenchymal stem cell is multipotent.

Cancer
1. Cancer is a group of diseases (around 200 in total) caused by a growth
disorder of cells.
2. It is the result of damage to the genes that regulate mitosis and the cell cycle,
which leads to unrestrained growth of cells.
3. As a result, a group of abnormal cells, called a tumour, develops and
constantly expands in size.
Cancer and the genetic control of cell division
1. Cancer cells are derived from a single mutant cell.
2. The initial mutation causes uncontrolled mitosis in this cell.
3. A further mutation in one of the descendent cells leads to other changes that
cause subsequent cells to be different from normal in growth and appearance.
4. In the process, a number of factors that regulate cell division are altered:
Oncogenes are mutated forms of the proto-oncogenes that regulate normal
cell division. Oncogenes can trigger uncontrolled cell division in the
following ways:
- permanently activating the receptor protein, even without the presence
of growth factors.
- producing excessive amounts of the growth factor.
Tumour suppressor genes, such as p53, code for proteins that stop the cell
cycle an also destroy mutated cells. A mutated p53 gene fails to do this and
so damaged DNA continues to divide, passing its mutations to daughter
cells.
Telomeres are non-coding regions of DNA at the end of chromosomes.
They are essential for DNA replication but, every time a cell divides, they
get shorter. This means that normal cells cannot divide indefinitely. In
cancer cells the telomeres do not shorten, no matter how many times the
cells divide, and they are therefore considered immortal.

Comparison of benign and malignant tumours

Primary and secondary tumours

1. Primary tumours
masses of abnormal tissue in their place of origin.
can be large and develop their own blood supply.
since they are localized, treatment of these tumours is often very
successful.
2. Secondary tumours
arise from cells that break away from the primary tumour and migrate via
blood or lymphatic vessels.
this method of spreading is called metastatis.
cells that do not metastasise may spread by growing rapidly, extending the
tumour into nearby tissues.