Last lesson we looked at: What is the definition of a gene?

Last lesson we looked at:

• What is the definition of a gene?

Last lesson we looked at:

• How many nucleotide bases code for each amino acid?

And we looked at:

• What is a mutation?

• Mutations can arise any time the information on DNA is used i.e. in both DNA replication and when forming mRNA during protein synthesis

And we looked at:

• Give an example of a mutagenic agent?

And we looked at:

• What are the two types of mutation you need to know for A level?

In which type of mutation does one base take the place of another?In which type is a base removed from the DNA sequence?Which could lead to a change in all of the amino acids in the polypeptide chain?Which would lead to only one amino acid being changed?Which leads to a frame shift?Which may have no effect on the polypeptide chain as it codes for the same amino acid?

Key points:

• Swaps one nucleotide for another.

Could lead to:• a change in one

amino acid• No change in amino

acid• A shortened

polypeptide chain.

• A nucleotide is removed from the chain

• All of the other nucleotides are moved along one place (frame shift)

• There will be many different amino acids after that point, leading to a different polypeptide.

We finished with:

• Mutations can have both beneficial and non-beneficial effects.

• One of the main conditions caused by mutations is cancer.

• For more information and advice about cancer, here is a link to the Cancer Research UK site.

• http://www.cancerhelp.org.uk/about-cancer/index.htm

By the end of this lesson:

• You should know the role of proto-oncogenes and tumour suppressor genes.

• Know how oncogenes affect cell division.

• Know how a mutation in a tumour suppressor gene results in the formation of a tumour.

• Know why secondary tumours arise.

Control of Cell Division

• What is the process by which normal cells divide so growth and repair can occur?

• http://www.youtube.com/watch?v=WZdErhuLCtc&NR=1

Proto-oncogenes code for proteins that stimulate normal cell division.

A protein attaches to receptors on the cell surface membrane. This causes relay proteins in the cytoplasm to ‘switch on’ genes necessary for DNA replication.

What does a gene mutation in a proto-oncogene cause it to mutate

into?

• An oncogene

In what two ways do oncogenes affect cell division?

• The receptor protein on the cell surface membrane becomes permanently activated so cell division is switched on even if growth factors aren’t present.

• The oncogene may code for a growth factor, e.g. a hormone, that is produced in excessive amounts, again stimulating excessive cell division.

• (a growth factor is a

naturally occurring

molecule which stimulates

cell growth)

What is the result of a mutation in a proto-oncogene?

• A tumour or cancer may develop.

What is the result of a mutation in a proto-oncogene?

• Uncontrolled cell division - A tumour or cancer may develop.

A highly magnified view of brain tumour tissue. Tumour cells have large, irregular nuclei, a small cytoplasm and large variations in size and shape. The cells are arranged in a disorganised fashion.

By the end :

• You should know the role of proto-oncogenes and tumour suppressor genes.

• Know how oncogenes affect cell division.

• Know how a mutation in a tumour suppressor gene results in the formation of a tumour.

• Know why secondary tumours arise.

Tumour suppressor genes

• http://www.youtube.com/watch?v=iLK3jy-kGvs&feature=related

Tumour suppressor genes inhibit cell division when growth or repair is complete. They code for proteins that prevent uncontrolled cell division. They also promote programmed cell death (apoptosis) in cells with DNA damage that the cell cannot repair.

These proteins work in three ways:• they repair damaged DNA before it is replicated.• they ensure cell adhesion, making sure cells are anchored in the correct place – relevant to malignant tumours (see later)• they inhibit cell division.

How does a mutation in a tumour suppressor gene result in the

formation of a tumour?• A normal tumour suppressor gene

maintains a normal rate of cell division.• A mutation causes the tumour suppressor

gene to be inactive• Cell division increases formation of mutant

cells which may be structurally or functionally different from normal cells

• Mutated cells which survive may clone to form tumours.

• Proto-oncogenes and tumour suppressor genes work together to control cell division. In healthy cells, the activities of proto-oncogenes and tumour supressor genes are in balance.

• Problems arise when the genes mutate, so non-functional proteins are produced, or other control mechanisms break down so that cells divide uncontrollably.

Overall:Gene Involved :

Normal Role :Stops Cell DivisionStimulates Cell

Division

Proto-oncogene Tumour Suppressor

Gene

MutationMutation

OncogeneMutated Tumour Suppressor Gene

Rapid, uncontrollable Cell Division

Tumour/Cancer

Cells Can’t stop dividing

By the end of today:• You should know the role of proto-oncogenes

and tumour suppressor genes.• Know how oncogenes affect cell division.• Know how a mutation in a tumour suppressor

gene results in the formation of a tumour.

• What is a tumour and why do secondary tumours arise.

• A tumour is a group of one type of cell that is dividing rapidly and uncontrollably. The formation of a tumour might result from one, or only a few, genetic changes in a cell.

• Secondary tumours occur when some cells break away from the group and invade organs and tissues throughout the body. This called metastasis.

• (The change from tumour cells to cancer cells requires many more genetic changes. Thus, cancer does not usually result from a single gene mutation).

Remember:

• Not all tumours are harmful:

These do not spread from their point of origin

These are able to spread from their point of origin in the blood or lymph.

• If the proto-oncogene of a cell mutates into an oncogene, causing the development of a tumour, how might the inactivation of a tumour supressor gene contribute to the development of a tumour at a secondary site (secondary cancer)?

• Inactivation of the tumour supressor gene may result in cells not being anchored together properly allowing a cancerous cell to move from it’s site of origin to invade other secondary tissues.

• An inherited type of breast cancer involves a tumour suppressor gene called BRCA1 that has two alleles. A small percentage of women who inherit one mutated allele have a 60% chance of having breast cancer by the age of 50, and an 80% chance of developing it by the age of 70.

• Explain why the comparable figures for the women who inherit two normal alleles of the gene are much lower (2% and 7% respectively).

• Why does the risk of developing breast cancer in both groups of women increase with age?

• The normal allele is dominant to the mutant allele

• People who have inherited one mutant allele have a higher predisposition to breast cancer as they only need one mutation in the normal allele for full inactivation.

• Those with two normal alleles would need 2 mutation events to cause inactivation.

• As mutations are rare it will take a long time until both alleles become mutated therefore the chance of developing breast cancer would increase with age.

You should now be able to:

• Answer the questions on transgenic mice pg 225 Hodder text book.

• Answer the exam questions 1 and 2 on control of cell division.