Mutations, Gene Expression and Cancer Flashcards
What is differentiation
When stem cells become specialised cells
Totipotent
-occur for limited time
-in embryo
-divide by mitosis
-produce ALL cells (translate only part of DNA)
-express all genes
Pluripotent
-in embryo/ faetal stem cells
-divide by mitosis
-produce MOST cells
-differentiate into specialised cells
Multipotent
-adult stem cell
-differentiate into MANY cells
Unipotent
-most stem cells unipotent
-only produce FEW/ONE cell
-e.g. unipotent cells in heart differentiate into cardiomyocytes
Summary of stem cells
- only stem cells divide by mitosis
- differentiation of stem cells determined by gene expression, only certain parts DNA expressed, other genes inactive
- most of cells DNA not translated and genes not expressed
Application of stem cells to medical research
- producing tissues for skin grafts
- research into producing organs for transplant
- cure diseases like Parkinson
Limitation of Stem cells
stem cells may divide out of control, leading to the formation of a tumour
Explain what is meant by the terms totipotent and pluripotent.
- totipotent cells can give rise to a complete human/all cell types;
- pluripotent can only give some cell types;
Explain how cells produced from stem cells can have the same genes yet be of different types.
genes are switched {on / off} /active / activated ;
*correct and appropriate reference to factors /mechanisms for gene switching ;
* e.g. reference to promoters / transcription factors
Promoter region definition
base sequences upstream of a gene that control expression of that gene
Transcription factor definition
proteins, which when activated, bind to promoter region of a gene stimulating RNA polymerase to begin transcription of target gene
- Some TF bind to promoter and inhibit transcription
Structure of oestrogen
lipid soluble so can diffuse through phospholipid bilayer of cell membrane
Control of transcription
- Oestrogen diffuses through the phospholipid cell membrane
- Diffuses through nuclear envelope
- Binds to the ERa receptor
- CHANGES 3° STRUCTURE
- Release the transcription factor;
- Transcription factor binds to the DNA;
- At the promoter region;
- stimulates RNA polymerase to transcribe the gene.
- This increases transcription, so mature mRNA produced.
Describe the mechanism by which a signal protein causes the synthesis of mRNA
- signal protein binds to
- receptor on surface membrane;
- messenger molecule moves from cytoplasm and enters nucleus;
- activates transcription factor;
- binds to promoter region;
- RNA polymerase transcribes target gene;
Control of Translation
-SiRNA and MiRNA are complementary to mRNA
-causes destruction of mRNA
-prevents translation
Why might some mRNA still be produced
not all mRNA has been destroyed so some translation has occured
Define epigenetics
Heritable phenotype changes that do not involve alterations in the DNA sequence
How to inhibit transcription
increases methylation of DNA
decreased acetylation of histones
Methylation of DNA
- methyl group added to cytosine
- Methyltransferase is the enzyme that catalyses this methylation reaction
- preventing transcription factors from binding to the promoter
- prevents the activation of RNA polymerase and inhibits transcription
- gene expression is ‘silenced’
Acetylation of histones
Acetylation of histone molecules results in them becoming loosely packed
When unwound, the promoter regions are exposed and transcription factors are able to bind.
allows RNA polymerase to bind and the target gene can be transcribed.
How to increase gene expression
decrease methylation
increase acetylation
Types of tumour
Malignant- fast growing, non capsulated, do metastasise
Benign- slow growing, surrounded by capsule, do not metastasise
Genes that control cell division
a) PROTO-ONCOGENES which stimulate cell division (code for proteins that increase the rate of cell division)
b) TUMOUR SUPPRESSOR GENES which slow cell division (code for proteins that decrease the rate of cell division)
mutation within a proto-oncogene
become an ONCOGENE
This results in an over-stimulation of cell division, so that cell division is permanently switched on.
This results in a mass of cells known as a tumour.
mutation in a TUMOR-SUPRESSOR GENE
the gene becomes inactivated
it stops inhibiting cell division
so the rate of cell division increases
Epigenetic changes to a tumor suppressor gene
- If there is increased methylation of a tumour suppressor gene, the rate of cell division increases.
- If there is increased acetylation of a tumour suppressor gene, the rate of cell division decreases.
Epigenetic changes to an oncogene
- If there is decreased methylation of an oncogene, so the rate of cell division increases.
- If there is decreased acetylation of an oncogene, so the rate of cell division decreases
Describe how alterations to tumour suppressor genes can lead to the development of tumours.
Increased methylation
Mutation in tumour suppressor genes
Tumour suppressor genes are not transcribed
uncontrollable cell division;
Explain how the methylation of tumour suppressor genes can lead to cancer
- Methylation prevents transcription of gene;
- Protein not produced that prevents cell division
- No control of mitosis
How to develop new cancer drugs
- drugs that inhibit methyltransferases (e.g. by competitive inhibition).
- reduce methylation of a promoter and therefore allow transcription factors to bind.
- activate RNA polymerase and lead to expression of the tumour suppressor gene which codes for a protein that slows the rate of cell division.
Describe how altered DNA may lead to cancer
- DNA altered by mutation
- changes base sequence;
- of oncogene
- of tumour suppressor gene;
- change protein structure
- tumour suppressor genes produce proteins that inhibit cell division;
- uncontrolled cell division
- malignant tumour;
Compare the structure of dsRNA and DNA.
- Polynucleotides
- Contain Adenine, Guanine, Cytosine;
- Have pentose sugar
- Double stranded
