Mutations, Stem Cells and Cancer Flashcards
Examples of tumour suppressor genes
Off spec, paper 3
TP53
BRCA1
BRCA2
What are tumour suppressor genes
Genes that slow down cell division by coding for proteins that decrease the rate of cell division
Also code for proteins that repair mistakes in DNA
Also code for proteins that instruct cells to die (apoptosis) (off spec, paper 3)
List 3 mutagenic agents
High energy ionising radiation
DNA reactive chemicals
Biological agents
Explain the mutagenic agent of biological agents
Viruses and bacteria
Explain the mutagenic agent of high energy ionising radiation
Xrays/gamma/alpha/beta
Damage DNA base sequence
Chemicals interfere with DNA replication or structure
Explain the mutagenic agent of DNA reactive chemicals
Benzene, bromine, hydrogen peroxide, nitrous acid
Remove amine (NH2) group on cytosine in DNA, converting it to uracil
What are stem cells
Undifferentiated cells
Able to express all genes they have
Divide by mitosis OR differentiate into specialised cells
What do stem cells do
Differentiate into specialised cells
Mitotic cell division into more stem cells
Types of stem cells
Totipotent
Pluripotent
Multipotent
Unipotent
Totipotent
Stem cells that can differentiate into all specialised cells available from its genes
Zygote and early embryo (up to 8 cell stage)
Pluripotent
Stem cells that can differentiate into most types of cell
Embryonic and fetal stem cells
Multipotent
Found in all tissues and can differentiate into a number of cells
Somatic cells/adult stem cells
E.g bone marrow contains multipotent stem cells that can differentiate into various blood cells
Unipotent
Can only differentiate into one type of cell
Used in formation of single cell types
E.g cardiomyocytes
What happens to cells as they differentiate
Lose their totipotency and become limited in the sections of their DNA that they translate
Because during specialisation only genes required for essential processes in cell and those needed to produce proteins for specialised functions are expressed
iPS
Induced pluripotent cells
Lab grown pluripotent cells
Not identical to pluripotent stem cells but can self renew
Providing a limitless supply in medical research
Caution with using stem cells
May divide out of control
Leading to formation of a tumour
5 uses of stem cells
Producing tissue for skin grafts
Research into producing organs for transplants
Research into how stem cells become specialised
Research into cancer
Research into serious diseases and the use of stem cells to cure them (parkinsons)
Ethical concerns of stem cells (4)
Human status from contraception
Potential life/human being so murder
Embryo can’t give consent
Animals must be used in experiments prior to human trials
How can you turn somatic stem cells into desired cell
Convert into iPS
Stimulate to differentiate via hormones into desired cell
9 diseases that can be treated with stem cells
Heart damage/attack: Heart muscle cells
Muscular dystrophy: Skeletal muscle cells
Type 1 diabetes: Beta cells of pancreas
Parkinsons, MS, stroke, paralysis: Nerve cells
Leukemia, blood diseases: Blood cells
Burns, wounds: Skin cells
Osteoporosis: Bone cells
Osteoarthritis: Cartilage cells
Macular degeneration: Retina cells of eye
Promoter vs transcription factor
Promoter is one or more base sequences complementary to transcription factor, found upstream of gene and controls gene expression
Transcription factor is a protein that binds to the promoter when activated and stimulates RNA polymerase to begin transcription
Example of a transcription factor
Oestrogen receptor (ER alpha)
Explain the activation of transcription
1) Oestrogen diffuses through the cell surface membrane (lipid soluble)
2) Diffuses through nuclear envelope
3) Binds to complementary ER alpha receptor
4) Causing a conformational change in shape and releases transcription factor
5) T.f. binds to DNA at complementary promoter region
6) Allowing RNA polymerase to transcribe the gene
How is translation controlled
RNAi
RNA interference inhibits gene expression via inhibiting translation
Transcribed from cell DNA when needed to stop/slow synthesis of protein
Disadvantage of overproduction of a protein
Protein synthesis uses lots of ATP
Overproduction is a waste of valuable ATP
That could be used for other processes (e.g active transport)
What are the two types of RNAi and what do they do
miRNA (micro RNA) and siRNA (small interfering RNA)
Single strands of RNA
Bind to a protein in cytoplasm to form RISC which inhibits gene expression (complementary base sequence to part of specific mRNA molecule)
What is RISC
RNA Induced Silencing Complex
Formed when RNAi binds to a protein (enzyme) in cytoplasm
Inhibiting DNA gene expression by binding to complementary mRNA
How does RISC inhibit gene expression
Binds to complementary mRNA…
-Hydrolyses mRNA by RNA hydrolase, cutting it into fragments
OR
-Inhibits initiation of ribosomal translation (ribosome prevented from attaching to mRNA, mRNA hydrolysed)
Translation does not take place
Polypeptide not produced
EXPRESSION OF GENE IS SILENCED
How can protein still be produced if RNAi used
Not all mRNA hydrolysed so some translation still occurs
RNAi hasn’t bound to all mRNA so some translation still occurs
Epigenetics
Inheritable changes in gene expression
Without changes to their DNA base sequence
How is translation inhibited in epigenetics
Increased methylation of DNA
Decreased acetylation of histones
What is methylation
The addition of a methyl group to carbon 5 of a cytosine base
Via methyltransferase
Changing the structure of a promoter
So it’s no longer complementary to the transcription factor
Cannot bind and transcription inhibited
No RNA polymerase activation
Where does methylation occur
CpG Islands
Common at the 5’ end of many genes
Carbon 5 of cytosine base
What is acetylation
Addition of an acetyl group (COCH3) to leucine
Causing histone winding to losen
Can expose the promoter
Transcription factor can bind so allows RNA polymerase to transcribe target gene
Acetyl group transferred from Acetylcoenzyme-A
Where does acetylation occur
Amino acid leucine
On the tails of histone molecules (side branches)
From Acetylecoenzyme A
2 types of cancer
Benign
Malignant
Compare benign and malignant tumours
Benign cannot metastasise whereas malignant do
Benign surrounded by dense tissue capsule and remains a compact structure whereas malignant are not so grow finger like projections into surrounding tissues
Benign less likely to reoccur after treatment
How are iPS produced
Produced from human somatic cells using certain protein transcription factors
What two genes are in control of the rate of cell division
Proto-onco genes
Tumour suppressor genes
What are proto-onco genes
Stimulates cell division
by coding for protein that increases the rate of cell division
How can cancers cause damage
May damage organ concerned
May cause blockages/obstructions (e.g. blood flow)
May damage other organs by exerting pressure on them
Mutation in a proto-onco gene
Alters to become an onco gene
Causing overstimulation of cell division
Cell division permanently switched on
Mass of cells known as a tumour develops
Mutation in tumour suppressor gene
Gene becomes inactive
Stops inhibiting cell division
Rate of cell division increases
Mass of cells known as tumour form
Overmethylated tumour suppressor gene
Gene becomes inactive
Stops inhibiting cell division
Rate of cell division increases
Leading to mass of cells being produced (tumour)
Undermethylated onco gene
Gene becomes more activated
Cell division switched on
Rate of cell division increase
Function of stop codons
When read by ribosome during translation, translation stops
So final polypeptide chain detaches from ribosome
How do alterations in tumour suppressor genes lead to a tumour
Increased methylation of tumour suppressor gene
Mutation in tumour suppressor gene
Genes not transcribes/expressed
Resulting in uncontrollable cell division via mitosis
In microscopy, how do you find the mean … number per mm2
Measure the diameter of the field of view and calculate the area
Using a micrometre slide and eyepiece graticule
Count number of … in field of view in a large number of different fields of view
Selected at random
Calculate mean
Why doesn’t oestrogen affect other cells
Not all cells have the ERalpha receptor/oestrogen receptor
Link between sunbathing and cancer
Sun has UV radiation
Causes mutations in the genes responsible for controlling cell division
Why are people with a family history of cancer at an increased risk
May inherit onco genes
Giving a predisposition to cancer
Consequence of methylation to promoter
Causes change to the tertiary structure of the promoter
No longer complementary to the RNA polymerase and can’t bind to promoter
RNA polymerase isn’t activated
No transcription
No mRNA produced
How can altered DNA cause cancer
DNA altered by mutation Mutation changes base sequence Of gene controlling cell growth/division Of tumour suppressor gene Change in protein structure/non-functional protein Tumour suppressor gene codes for protein that inhibits cell division Mitosis Uncontrollable cell division Leading to a malignant tumour
