Genomes-L4-Oncogenes and Tumour Suppressors

2 things that influence the likelihood of cancer

1. exposure to mutagenic agents- such as blood, astral, lungs

2. rate of which tissues in cells are replaced- every round of replication is a chance for mutations

what tissues are most likely to get cancer?

tissues that experience the most damage- epithelial cells and gastrointestinal cells

• there is a high turnover rate

why does a high rate of cell division lead to mutations

• DNA polymerase- makes mistakes 1 in 100k bases- sometimes errors are found though

• more divisions- more chances for error

what have the highest rates of cancer?

lung, colon, breast, pancreatic and oesophageal

what causes cancer?

mutations in genes that regulate

• cell division

• cell death

what has to happen for cancer cells to become cancerous and immortalised? in normal circumstances what happens

need to proliferate more and not to die when its supposed to

• in normal: when a cell behaviours abnormally it is killed by activating own cell death machinery/patrolling cells do

types of mutations

1. silent- don’t affect anything

2. loss of function- changes amino- loss of function of the protein

3. gain a function- where you open amino acid active site- doesn’t need a ligand and is always on-ONCOGENIC

4. dominant interfering mutation- mutation doesn’t just affect protein but those around it

example of dominant interfering mutation

• consequence of mutation that also affects wild type

• P53 works as a tetramer- if one doesn’t work- all of them don’t work

what are passenger mutations

• they can occur as a result of DRIVER mutations

• mutations resulting from other mutations

what are driver mutations (important)

these are the mutations that drive cells towards transformed state- usually gain a function

• usually gain a function in growth factors

• turn off genes that suppress genes

what are oncogenes

a gene in its mutated form that promotes cancer

• gain of function and increase activity or expression level of a gene product

what are tumour suppressors genes

• usually act to oppose cancer

• usually are inactivated and don’t carry normal function

• loss of function genes

what does monoclanatlic mean in relation to cancer?

cancer is from one progenitor cell- one originator cell

• tumours then develop sub clones with more mutations

• b cell lymphonas- each B cell makes a unique antibody

mutation effects in proteins: bike analogy? what does this say?

• mutations affect different parts in different ways

• saddle- bike works but less comfortable- weak loss

• no lights- fine but dangerous- conditional loss

• deflated tie- slow down but works

• remove a wheel-complete loss of functions

mutations affect proteins depending where they hit!!!

genes in body- what changes in mutations in promotor?

• if no promotor- gene cant be expressed

• if mutated- can express protein/mRNA more

what happens to cell when they divide withoutt permission?

• if cells express proteins never seen before- mutation- will be killed

• cell migrates to far- will die- detached from matrix and die