pro euk lll

Question 1

function of checkpoints in the cell cycle

Answer 1

G1: passed if DNA is not damaged
G2: passed if DNA is not damaged, chromosomes have replicated and sufficient cyclins have accumulated
M: passed if all chromosomes are attached to spindle fibres from both poles

Question 2

causative factors which increase chances of cancer

Answer 2

A. Environmental factors  exposure to carcinogens (eg. tar in cigarette smoke, asbestos etc.) and ionizing radiation (e.g. uv radiation, X-rays) can cause mutations that lead to cancer

B. Loss of immunity due to infection with certain viruses  HIV can weaken the immune system and reduces the body’s ability to fight infections by other viruses that can cause to cancer.

C. Genetic predisposition  due to gene mutations (in the germ cells) which we inherit from our parents
D. Age  chances of getting cancer increases with age due to accumulation of mutations in a cell over a lifetime

Question 3

examples of carcinogens and ionising radiation

Answer 3

carcinogens: tar in cigarette smoke, asbestos
ionising radiation: uv radiation, x-rays

Question 4

what are proto-oncogenes

Answer 4

1. code for proteins (e.g. growth factors, activators, growth signal transduction factors) that stimulate normal cell division/proliferation
2. when mutated, they are known as oncogenes
3. contribute to cancer by gain-in-function mutations

Question 5

how can oncogenes cause cancer by point mutation

Answer 5

by a point mutation in base sequences of regulatory elements coded for by the proto-oncogene (e.g. stronger promoter created)
This can lead to increased frequency of transcription, and excess production of the proto-oncogene protein product (e.g. growth factor) and can lead to uncontrolled cell division

Question 6

how can oncogenes result in cancer by gene amplification

Answer 6

the number of copies of a proto-oncogene in a cell is increased due to a mistake made during DNA replication
This can lead to excessive production of proto-oncogene protein product (e.g. growth factor) and can lead to  uncontrolled cell division

Question 7

how can oncogenes result in cancer by chromosomal translocation

Answer 7

(iii) chromosomal translocation involving unusual exchange between chromosomes, such that the proto-oncogene ends up under the control of a enhancer
This can lead to excessive production of proto-oncogene protein product (e.g. growth factor) and can lead to  uncontrolled cell division

Question 8

how can oncogenes result in cancer as a result of retroviral integration

Answer 8

when a provirus integrates into the host chromosome, it
1) can inactivate a silencer of a proto-oncogene
2) can result in the insertion of a viral genome that contains a enhancer, upregulating expression of a proto-oncogene
3) can insert a viral homologue of proto-oncogene
All 3 events can lead to excessive production of proto-oncogene protein product (e.g. growth factor) and can lead to  uncontrolled cell division

Question 9

how can oncogenes increase the intrinsic activity of the proto-oncogene product and cause cancer

Answer 9

point mutation occurs within the proto-oncogene
This changes the amino acid sequence of the proto-oncogene protein (e.g. growth factor) which can then become hyperactive or more resistant to degradation and can lead to
 uncontrolled cell divison

Question 10

example of proto-oncogene

Answer 10

e.g. ras gene: mutation in the ras gene results in a constitutively active Ras protein that irreversibly binds to GTP and increases cell division even in the absence of growth factors

Question 11

what are tumour suppressor genes

Answer 11

codes for protein products that inhibit cell division and prevent uncontrolled cell division or by activating cell cycle arrest, DNA repair and/or apoptosis.
cause cancer when it undergoes loss-in-function mutation

Question 12

role of protein products that are coded for by TSG

Answer 12

(a) cell cycle arrest: gives the cell enough time to repair damaged DNA and prevent formation of mutant daughter cells
(b) DNA repair: prevents mutations that may lead to the formation of oncogenes or inactivated tumour suppressor genes
(c) initiating apoptosis (programmed cell death) when DNA damage is beyond repair: which will thus remove cells with damaged DNA with the potential to cause cancer

Question 13

role of p53 gene (type of TSG)

Answer 13

codes for specific transcription factor p53 protein that binds to DNA to promote synthesis of cell-cycle inhibiting proteins, so p53 protein functions as activator

Question 14

what happens when a TSG is mutated?

Answer 14

get inactivated and do not code for genes coding for protein products that inhibit cell division
cell proliferation is not restricted and cell cycle continues without DNA being repaired, mutations accumulate over time and cancer cells have a higher chance of developing

mutations occur in promoter or coding sequence of gene

Question 15

why is a gain in function mutation dominant

Answer 15

 mutation in just one copy of the allele results can result in uncontrolled cell division due to the increased synthesis/activity of a functional product (which was not produced
previously) due to mutation.

since only one copy of the allele needs to be mutated, the mutation is said to be dominant.

Question 16

why is a loss in function mutation recessive

Answer 16

mutations in both copies of the allele necessary for the loss-of-function phenotype to be observed.
 even when one copy is mutated, the non-mutant copy still produces a functional gene product.
Thus the non-mutant copy will mask the effect of the mutant copy and hence the mutation is said to be recessive.

Question 17

why is development of cancer a multi step process

Answer 17

The development of cancer requires the accumulation of mutations in the genes which control regulatory checkpoints of the cell cycle in a single cell
This will disrupt the normal cell cycle, thus causing the cell to undergo excessive cell proliferation
A gain-in-function mutation is a dominant mutation where mutation in just one allele of a proto-oncogene will result in its overexpression which will result in the production of excessive amounts of
growth factors or hyperactive/degradation resistant growth factors leading to excessive cell proliferation
Loss-of-function mutation is a recessive mutation where mutations in both alleles of a tumour suppressor gene will result in the non-functional/missing protein which will disrupt their ability to
inhibit cell cycle, enable DNA repair and promote apoptosis
Activation of the genes coding for telomerase result in telomeres being lengthened allowing the cell to dividing indefinitely as the chromosomes are prevented from shortening with each DNA
replication cycle.
Loss of contact inhibition* will enable the cells to grow into a benign tumour (mass of cells).
 Angiogenesis occur within the tumour so that the blood vessels formed can transport oxygen and nutrients for its growth.
The presence of blood vessels can result in the formation of a malignant tumour capable of metastasizing to other parts of the body via the bloodstream to form secondary tumours
As it takes years to accumulate these mutations, the chances of developing cancer increases with age.