The cell cycle

Life depends on a flow of cells (and DNA)

Multicellular organisms start off as a single cell, which then divides and each cell produced then grows to a certain size. The cell division process continues for some time but slows down or ceases when tissues are formed and are functioning efficiently in the living organism. In an adult organism, only a few cells are able to divide.

Eukaryotes (higher plants and animals, and fungi) have genetic material (DNA) associated with proteins to form chromosomes inside nuclei in all of their cells, and it is important that this DNA is copied and distributed equally into all the cells.
There are a small number of eukaryotes that only exist as single cells (e.g. Amoeba and other unicellular protoctists), but they also have a nucleus containing chromosomes and DNA.

Prokaryotes (Bacteria, Cyanobacteria and Archaea) also have DNA - in the form of a loop - as their main genetic material, but it is not associated with protein and there are no chromosomes or nuclei. There may also be smaller independent loops of subsidiary genetic material in the form of plasmids - which may contain genes for other features such as resistance to a particular antibiotic.
Prokaryotes exist as single cells, considerably smaller than eukaryotic cells, and with limited internal components. But under ideal conditions these microorganisms can reproduce quickly by cell division and so they may be found in large numbers.

Viruses do not have a structure based on cells. They are smaller than prokaryotic cells and they consist of nucleic acid (some have DNA, some have RNA) inside a capsid (protein coat), but they do not contain any other cellular structures (organelles).

Which came first?

A hen is only an egg's way of making another egg.

Samuel Butler

One of the central tenets of cell theory

Omnis cellula e cellula
All cells (arise) from (other, pre-existing) cells
Rudolf Virchow

Cells multiply by dividing

Before a eukaryotic cell divides, it must make copies of all the important components: mitochondria, chloroplasts (plant cells only), ribosomes and of course its genetic material. It can only grow in size by a small amount but after division it must make itself up to the normal size. Many of these changes are not easy to see, even with a microscope, but events concerning the nucleus are the most obvious changes inside the cell.

Going through the phases

The cell cycle consists of a number of stages or phases which gradually change into the next in the sequence. The name interphase is given to a period of time when the cell appears 'normal', in between the stages of nuclear division - mitosis.

Variation in the quantity of DNA in a cell during the cell cycle

There are three stages within interphase: the first gap phase G1, the synthesis phase S, and the second gap phase G2. In cells that are no longer dividing there is a sort of switch or restriction point within G1 that may not be passed. These cells are said to be in phase G0, and this is the normal situation in mature body cells which have become differentiated for their final function.

Interphase stage	Events within cell
G1	Chromosomes consist of nucleosomes (DNA wound on histone). Nucleus stains indistinctly as chromatin.
S	DNA replicates. Centrioles divide.
G2	Spindle protein subunits and histone synthesised

The cell cycle

Stages of cell division in a garlic root

(counts from a "root tip squash")

Stage	Number of cells
Interphase	872
Prophase	74
Metaphase	18
Anaphase	10
Telophase	8

These numbers can be used to estimate the time taken in the various stages, and to calculate the mitotic index: the ratio of the number of cells undergoing mitosis to the number of cells not undergoing mitosis (i.e. in interphase).

Within the cell cycle, mitosis is the name given to nuclear division, and it consists of a number of phases: prophase, prometaphase, metaphase, anaphase and telophase.

Cytokinesis (division of the cytoplasm) is normally next, resulting in two cells.

Each of the cells produced after mitosis is genetically identical.

Mitosis phase	Events within cell
Prophase	Chromosomes become shorter and thicker (condensation) and absorb stain strongly.. Under the light microscope, they can be seen to be double (composed of 2 chromatids). Mitotic spindle - a structure composed of protein fibres - forms between centriole pairs, which gradually move apart.
Prometaphase	Nuclear membrane disintegrates. Spindle occupies central section of cell - from pole to pole. Centromeres (near middles of chromosomes) radiate kinetochore filaments which attach to the spindle.
Metaphase	Chromosomes become aligned with centromeres across equator of cell, attached to the spindle. Viewed from the side, they form a fairly distinct line; from other angles they can be seen as a metaphase plate.
Anaphase	Two sets of chromosomes move apart in opposite directions. Distinctive V shapes are formed, pointing towards poles.
Telophase	Nuclear membranes re-form around the 2 separate sets of chromosomes. Chromosomes uncoil and decondense.
Cytokinesis	Cleavage furrow forms across cell equator. Cytoplasm divides and two daughter cells separate.

Practical work observing stages of mitosis

This usually involves

• the preparation of stained squashes of cells from plant root tips
• set-up and use of an optical microscope to identify the stages of mitosis in these stained squashes
• calculation of a mitotic index
• measurement of the apparent size of cells in the root tip
• calculation of their actual size using the formula:
Actual size = size of image / magnification

This is generally seen as 'required' practical work - see web reference below.

The microtubule-organizing center (MTOC)

is a structure found in eukaryotic cells from which microtubules emerge. Its main function is the organization of the spindle apparatus, which separates the chromosomes during cell division after mitotis (and meiosis).
[Another type of MTOC: the basal bodies associated with cilia and flagella].
In animal cells, the MTOC associated with spindle formation is the centrosome, which consists of 2 centrioles.

Proteins involved in the spindlle

Microtubules are composed of tubulin, which is built up from α and β sub-units to form hollow tubules.

Within the cell, astral filaments radiate from the MTOC towards the cell membrane at each pole of the cell. Other filaments move into the centre of the cell. K-fibres radiate from the kinetochores which spread our sideways from the centromere regions of the chromosomes.

Each tubule has a polarity ('plus' and 'minus' ends), and subunits are added to one end of the microtubule. Other motor proteins powered by ATP move along the microtubules causing movement in one direction or another.

Kinesins move in a walking action, usually towards the positive end of a microtubule.

Dyneins are motor proteins that move along microtubules, towards the minus-end.

Cytokinesis involves actin and myosin

[Actin and myosin are proteins which move relative to one another in muscle fibres.]
A contractile ring of actomyosin forms in the centre of the equatorial region of the cell, on the inner edge of the cell membrane. This causes the cleavage furrow which pinches the cytoplasm into two and brings the cell membrane in as well.

Cancer is caused by uncontrolled cell division

If body cells divide out of normal control, they become known as cancer.

Some cancers consist of a mass of unwanted cells called tumours. They may damage surrounding tissue.

So-called benign tumours have a slower rate of cell division and may become surrounded by a fibrous capsule so they remain in one place within the body.

Malignant tumours consist of cells which divide faster so they tend to break off and spread through the blood and bodily fluids to other tissues, forming secondary tumours. This is called metastasis.

Cancers are caused by chemical or physical damage to DNA or by viruses which interact with cellular DNA.

The name cancer is based on the appearance of blood vessels growing round the outside of a tumour, looking like a crab's claws.

This development of abnormal arteries and veins - angiogenesis - is caused by the release of chemical growth factors from the cells of the tumour, and this causes ordinary blood vessels to divide and provide the tumour cells with nutrients and oxygen.

Bringing cell division back under control by chemotherapy

Many cancer treatments are directed at controlling the rate of cancer cell division, but they may have side-effects on normal body cells. This may be performed by introducing chemicals which interfere with DNA replication, or those that prevent formation or functioning of the spindle.


5 Fluorouracil (5FU) is a compound which is fairly similar to thymine. It has a fluorine atom where thymine has a methyl group.
It can be described as a thymine analogue, and is used as an anti-cancer drug.
It acts as a selective inhibitor of an enzyme that incorporates thymidine phosphate into DNA which dividing cells, especially cancer cells, need for growth.

Tubulin inhibitors

are substances that prevent the formation of the mitotic spindle.

Colchicine (an extract from the Autumn Crocus Colchicum autumnale sp) has been used to interfere with cell division and cause polyploidy in certain crop plants. This is quite a toxic chemical.

However other compounds have been used medicinally to prevent cell division in order to fight cancer.

Vinblastine and vincristine are alkaloids isolated from leaves of the rosy periwinkle/Madagascar periwinkle plant Catharanthus roseus (Vinca rosea). These compounds have been described as tubulin polymerization inhibitors. They have been used against Hodgkin's lymphoma, non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer.

Side effects include reduced blood cell production due to bone marrow suppression , gastrointestinal toxicity and other effects to do with reduced cell division.

Taxol AKA paclitaxel, is a compound originally obtained from the bark of the Pacific Yew tree Taxus brevifolia. It prevents the dynamic activity of tubulin in the separation of chromosomes, and effectively over-stabilises the tubulin structure. Its action is described as a depolymerization inhibitor.

Kinesin inhibitors

Substances called kinesin inhibitors (KI) have been considered as potential treatments for cancer. Some kinesin inhibitors cause the development of an abnormal monopolar spindle in mitosis, preventing successful mitosis and hence cell division.
This is because there is no separation of chromatids, so they all go to one end of the cell, and this gives double the normal number of chromosomes in the cell, and possibly one daughter cell will get none.

Binary fission in prokaryotic cells

This means 'splitting into two'.

Before this happens the main circular DNA and the DNA of any plasmids (if present) must replicate itself, although these events are not synchronised in any way.
The two strands of each DNA molecule peel apart to allow semi-conservative replication. This is essentially the same process as in eukaryoyes, but without any protein on which to wind up the DNA afterwards.

Extra copies of some cell components, e.g. ribosomes, must also be produced.

This is followed by division of the cytoplasm to produce two daughter cells. Each of these receives a single copy of the main circular DNA and possibly a variable number of copies of plasmids. Each cell then grows in size following the intake of nutrients from the surrounding medium.

Bacterial cells in the process of division

Diffuse blobs of DNA show up in light green and other cell components can be seen in lighter blue.

Viral replication

Viruses depend on the cells of their host for replication. Being technically not living and non-cellular, they themselves do not undergo cell division.

Following injection of their nucleic acid (DNA or RNA) into the host cell, new virus particles are produced using the internal enzymes and organelles of the infected host cell. Their component parts - mostly nucleic acid and protein subunits of their outer coat - spontaneously assemble themselves in the cytoplasm so that many copies of the original virus particle are released when the host cell bursts.

Tobacco mosaic virus

The capsid is built up from a number of identical protein units (blue), and the nucleic acid - RNA (gold) runs through a groove in this cyindriacl structure.