Gene Expression Flashcards
Gene Mutations
what is a gene mutation?
a change/alteration in the base sequence of a gene, which can cause a change in the polypeptide chain. it is caused by errors that occur during DNA replication.
what are the 6 types of gene mutations?
- substitution
- deletion
- addition
- duplication
- inversion
- translocation
what happens when there is a change in the base sequence of DNA?
if the amino acid sequence changes, then the protein is modified, there is a change in the tertiary structure, different hydrogen and ionic bonds will form in different places and fold differently. this will result in a different 3D shape and result in a non-functioning protein.
what can increase the chance of a mutation occurring?
mutagenic agents
what are some mutagenic agents?
- high energy and ionising radiation - alpha and beta particles ,x-rays, gamma rays, UV radiation
- carcinogens - tobacco smoke, mustard gas
UV radiation is not ionising but able to cause damage to DNA?
is not ionising but is high enough to cause damage and disrupt the structure of DNA
wat is a carcinogen?
this is the term given to chemicals that can alter the structure of DNA and interfere with transcription. these
Which main ways can a mutagenic agent increase the rate of mutations?
- acting as a base - chemicals called base analogs can substitute for a base during DNA replication
- some chemicals can delete or alter bases
- some radiation can change the structure of DNA, which causes problems during DNA replication.
What are the 6 different types of mutations?
- substitution
- addition
- deletion
- duplication
- inversion
-Translocation
What is Addition/ insertion mutation?
Where one or more bases are added to base sequence of DNA, this causes a frameshift to occur
what is a deletion mutation?
A base is deleted/removed from the base sequence of DNA. this also causes a frameshift to occur
what is a substitution mutation?
one or more bases are replaced/swapped for another base in the base sequence of DNA. May not result in a non-functional protein, due to the genetic code being degenerate and only one codon is affected.
what is a duplication mutation?
one or more bases are repeated in the base sequence of DNA. This produces a frameshift to the right.
what is an inversion mutation?
a group of bases become detached/separated from the base sequence of DNA and rejoin at the same position but in the inverse order (back to front). Therefore codes for a different amino acid.
What is a translocation mutation?
a group of bases become separated from the base sequence of DNA on one chromosome and become inserted onto the base sequence of DNA on another chromosome.
What happens if the amino acid changes?
if a single amino acid is changed to a similar one (both small and uncharged), then the protein structure and function may be unchanged, but if the amino acid is changed to a very different one (e.g an acid group to a basic group), then the structure and function of the protein will be very different.
why are mutations like addition and deletion more harmful?
Cause a frameshift in the base sequence of DNA, so are far more serious because the protein is altered.
if the frameshift is at the end of the gene, will the effects be more or less serious?
less serious
Why might the mutation not be expressed?
- may be present in non-coding parts of DNA
Describe how mutations affect somatic cells (non-reproductive cells)?
mutations in non-reproductive cells (i.e non-reproductive body cells) will only affect the cells that derive from that cell, so will probably have a small effect like a birthmark (although can cause widespread effects like diabetes or cancer)
Describe how mutations affect Germ cells (reproductive cells)?
Mutations in Germ cells will affect every single cell of the resulting organism, as well as the offspring. These mutations are one source of genetic variation.
what are the three phenotypic effects of mutations?
- no phenotypic effect
- negative phenotypic effect
- positive phenotypic effect
what are mutations that don’t have a phenotypic effect called?
Silent mutations, and well all have a few of these
which mutations generally have a negative phenotypic effect?
most of protein in cells are enzymes, and most changes in enzymes will stop them working. When an enzyme stops working, a metabolic block can occur, when a reaction in a cell doesn’t happen, so the cell’s function is changed.
Give an example of this?
An example of this is PKU (phenyketonuria), caused by a mutation in the gene for the enzyme phenylalanine hydroxylase. This causes a metabolic block in the pathway involving the AA phenylalanine, which builds up causing mental issues.
When could a mutation have a positive effect?
very rarely a mutation can have a a positive effect such as making an enzyme work faster, or a structural protein stronger, or a receptor protein more sensitive. Although rare beneficial mutations are important as they drive evolution
Stem cells
what is cell differentiation?
the process by which each cell develops into a specialised structure suited to the role that it will carry out.
what do all multi-cellular organisms have?
all have a range of specialised cells which each have a specific dunction
where do these specialised cells originate from?
from undifferentiated stem cells
What are stem cells?
stem cells are undifferentiated cells that can continually divide and become specialised, they can self-renew
by which process do stem cells become specialised?
Differentiation
Describe how stem cells become specialised?
Stem cells become specialised by only expressing certain genes and switching off others. Genes that are expressed get transcribed into mRNA, which is then translated into proteins. These proteins modify the cell. Changes to the cell produced by the proteins cause the cell to become specialised.
where are main sources of stem cells found in mammals?
- embryonic stem cells (embryo’s)
- adult stem cells (adult tissue)
- umbilical cord blood stem cells
- placental stem cells
what are embryonic stem cells?
embryonic stem cells come from embryos in the early stages of development. they can differentiate into any type of cell in the initial stages of development
How can embryo’s be obtained?
Embryo’s are created in a lab by using In Vitro fertilisation (IVF) - egg cells fertilised by sperm cells outside the womb, once the embryo’s are 4-5 days old, stem cells are removed from them and the rest of the embryo is destroyed.
what are umbilical cord stem cells?
umbilical cord blood stem cells are derived from the umbilical cord blood and are similar to adult stem cells
what are placental blood cells?
placenta blood cells are found in the placenta and develop into specific type of cells
What are adult stem cells?
adult stem cells are found in the body tissues of the fetus through to the adult. they are specific to a particular tissue or organ within which they produce the cells to maintain and repair tissues throughout an organisms life.
Most of these Stem cells have been found in the blood, bone marrow, liver, kidney, cornea, dental pulp, umbilical cord, brain, skin, muscle, salivary gland
How can stem cells be classified?
According to their potency
what is potency?
the ability to differentiate into specialised cells
what are the different types of potency stem cells can be classified by?
- Totipotency
- pluripotency
- multipotent
- unipotent
What are totipotent stem cells?
totipotent stem cells are found in embryo’s and can differentiate into any type of cell. Since all body cells are formed from a zygote, it follows that the zygote is totipotent. As the zygote divides and matures (e.g into a blastocyst), it’s cells develop into slightly more specialised cells called pluripotent stem cells
what are pluripotent stem cells?
pluripotent stem cells are found in embryo’s and can differentiate into almost any type of cell. (embryo’s up to 16 days after fertilisation contain pluripotent stem cells)
what are examples of pluripotent stem cells?
embryonic stem cells and fetal stem cells
what are multipotent stem cells?
are found in adults and can differentiate into a limited number of specialised cells. They usually develop into cells of a particular type, for example, stem cells in the bone arrow can produce any type of cell.
what are examples of multipotent stem cells?
adult stem cells and umbilical cord stem cells
what are unipotent stem cells?
Unipotent stem cells can differentiate into a single type of stem cell. they are derived from multipotent stem cells and are made into adult tissue.
what is an example of Unipotent stem cells?
An example of unipotent stem cells are cardiomyocytes. these are heart muscle cells that divide to produce new heart tissue, and so repair damage to heart muscle
Induced pluripotent stem cells
What are iPS cells?
Induced pluripotent stem cells
What are induced pluripotent stem cells?
iPS cells are a type of pluripotent stem cells that is produced from Unipotent stem cells (which can form any type of body cell). These body cells are then genetically altered in a laboratory to make them acquire the characteristics of embryonic stem cells (pluripotent cells)
How are iPS cells produced?
- iPS cells are created from unipotent stem cells. These cells are altered in a lab to return them to a state of pluripotency
- to do this, the genes are switched off to make the cell specialised, must be switched back on
- this is done using transcriptional factors
- this is very similar to embryonic stem cells, but do not cause the destruction of the embryo and the adult can give permission
- the iPS cells are able to self-renew, in that they divide indefinitely to give infinite supplies
Explain how transcription factors allow the adult stem cells (that was unipotent) to become pluripotent?
- adult body cells become reprogrammed so they become pluripotent
- the adult cells are made to express a series of transcription factors that are normally associated with pluripotent stem cells.
- the transcription factors cause the adult body cells to express genes that are associated with pluripotency
Describe one way in which Transcription factors be introduced to adult body cells?
- one of the ways that these transcription factors could be introduced to the adult cells if by infecting them with a specially-modified virus.
- The virus has the genes coding for the transcription factors within it’s DNA. When the virus infects the adult cell, the genes are passed into the adults cell’s DNA, meaning that the cell is able to produce the transcription factors
Why is the use of iPS cells more liked than using embryonic stem cells?
- ethical issues surrounding embryonic stem cells are removed
- do not cause the destruction of the embryo
- the adult can give permission (whereas the embryo cannot)
- iPS cells can be made from the individuals own cells, so could be used to grow new tissue and remove issue of tissue rejection.
- the iPS cells are able to self-renew, in that they divide indefinitely to give infinite supplies
Why is the use of Embryo’s have ethical issues/ Issues with Stem cell research?
- obtaining stem cells from embryo’s creates ethical issues because the procedure results in the destruction of the embryo that could have become a fetus if placed in the womb
- people also argue that the embryo deserves the same respect as human life
- very costly
what is the other opinion?
- the embryo is just a ball of undifferentiated cells, bearing no resemblance to human beings
- sufficient protection from the law against cloning
What are the Overall benefits of stem cells therapy?
- they could save many lives - e.g many people waiting for organ transplants die before the transplant. Stem cells could be used to grow organs for people awaiting transplants
- Stem cells can be made to be genetically identical to patients, so remove issue of tissue rejection
- Stem cells allow us to study how organisms grow and develop over time.
- Stem cells can replace diseased or damaged cells that can not heal or renew themselves.
- We can test different substances (drugs and chemicals) on stem cells.
- We can get a better understanding of our “genetic machinery.”
Regulation/ Control of transcription and translation
In Eukaryotes, How can transcription be stimulated or inhibited?
when specific transcriptional factors move from the cytoplasm into the nucleus
what can this do?
This can turn on/off genes, so only certain proteins are produced in a particular cell
what does turning on or off genes do?
turning on or off genes in a particular cell is what enables them to become specialised.
What are the 4 categories in which DNA expression can be controlled?
- Transcriptional (transcriptional factors and
oestrogen) - Post-transcriptional (siRNA)
- Translational
- Post-translational
What are transcriptional factors?
transcription of a gene will only occur when a molecule from the cytoplasm enters the nucleus and binds to the DNA in the nucleus, called promoters. These molecules are called transcriptional factors
Where are promoters found?
promoters are found near the start of their target genes , the genes they control the expression of.
What are activators?
some transcriptional factors are called activators, stimulate or increase the rate of transcription - e.g they help RNA polymerase bind to the start of the target gene and activate transcription
What are repressors?
transcriptional factors that inhibit or decrease the rate of transcription - e.g they bind to the start of the target gene, preventing RNA polymerase from binding, stopping transcription.
Each transcriptional factor can bind to what..?
each transcriptional factor can bind to a specific base of the DNA in the nucleus and therefore begin/initiate transcription
what is produced?
Messenger RNA is produced and the information it carries is translated into a polypeptide in the cytoplasm.
so when the transcriptional factor is turned on/ bound (to DNA in the nucleus), what is able to happen and be made?
- this means that RNA polymerase is able to bind DNA, therefore mRNA sequence is created. and so can move into the cytoplasm attached to a ribosome and the polypeptide chain/ protein is created.
so when a gene is switched off/ not expressed..?
the site on the transcriptional factor that binds to DNA is not active
As the site on the transcriptional factor binding to DNA is inactive, which processes can not be initiated?
it cannot cause transcription and translation
which Hormone is able to switch on the gene and thus start transcription?
Oestrogen which is a steroid hormone.
Describe the effect of oestrogen on a transcriptional factor?
- Oestrogen is a lipid soluble molecule and therefore diffuses easily through the phospholipid portion of the cell-surface membranes
- once inside the cytoplasm of the cell, oestrogen binds to it’s receptor site on the ERα transcription factor. the shape of the site and the shape of the oestrogen molecule complement one another
- there is a change in shape of the ER transcription factor
- The ER releases it’s Inhibitor molecule and becomes activated, moving into the nucleus of the cell
- Using it’s DNA binding site, the ER binds to the sequence of DNA found upstream of the promoter region
- The ER acts as an enhancer, promoting the recruitment of RNA polymerase to the promoter region
- RNA polymerase binds to the promoter region and initiates the uncoiling of the gene
I think after this it’s uneccessary? - DNA helicase breaks the hydrogen bonds and leaves exposed bases on the two strands of DNA
- Free RNA nucleotides move in and line up opposite the exposed bases on the template strand and form temporary hydrogen bonds with their complimentary bases
- Moving in 5’ to 3’ direction, the RNA polymerase requires energy to form phosphodiester bonds that link adjacent RNA nucleotides
- mRNA synthesis stops as soon as the RNA polymerase reaches the terminator region
- the pre-mRNA detaches from the DNA and moves to the splicesome for splicing and removal of introns
Describe the effect that Oestrogen has on transcription factors?
- Oestrogen is a lipid soluble molecule and therefore diffuses easily through the phospholipid portion of the cell-surface membranes
- once inside the cytoplasm of a cell, oestrogen binds with a site on the receptor molecule of the transcriptional factor. the shape of the site and the shape of the oestrogen molecule are complimentary to on another
- By binding with the site, the oestrogen changes the shape of the DNA binding site on the Transcriptional factor, which can now bind DNA (it is activated)
- the transcriptional factor can now enter the nucleus through a nuclear pore and bind to specific base sequences on DNA
- the combination of the transcriptional factor with DNA stimulates the transcription of the gene that makes up the portion of DNA
Epigenetics
What is Epigenetics? - MSA
Heritable changes in gene function, without changing the base sequence of DNA. These changes are caused by changes in the environment and can inhibit transcription
Explain Epigenetics in terms of genotype and phenotypes?
a change in phenotype without a change in genotype
How is Epigenetics controlled?
This works through the attachment or removal of chemical/epigenetic marks to or from DNA or Histone proteins?
Give two examples of Epigenetic marks?
- Methyl groups on DNA
- acetyl groups on histones.
What can Epigenetics be influenced by and how?
Factors such as: Stress ageing, drugs, diet , stress, toxins, eating habits can add epigenetic tags/marks to the DNA and controls gene expression in eukaryotes
What is DNA wound around?
Histone proteins
What are these sometimes covered in and what do they form?
Chemical marks. These chemical marks sometimes form a single/second layer known as the epigenome
What does the Epigenome do?
Determines the shape of the DNA-Histone complex, and whether DNA is tightly wound around histones
- For example it keeps genes that are inactive in a tightly packed arrangement and therefore ensures that they can not be read (switched off). - (A.K.A epigenetic silencing)
- In contrast, also unwraps active genes so that DNA is exposed and can easily be transcribed (switches them on)
If DNA is tightly wounded, why can it inhibit transcription?
Because transcriptional factors are unable to bind
what is the difference between DNA and the epigenome?
DNA code is fixed, wheras the epigenome if flexible
Why is the Epigenome considered to be flexible and DNA code to be fixed?
this is because it’s chemical tags respond to environmental changes. So factors like stress and diet can cause the chemical tags to adjust the wrapping of the DNA and so switch genes on and off
What are the two main ways that Transcription can be inhibited?
- Decreased Acetylation of Histone proteins
- Increased methylation of DNA
when the association of histones with DNA is weak, the DNA - Histone complex is…?
less condensed (loosely packed). DNA is accessible by transcriptional factors, which can initiate production of mRNA, so can switch on the gene
when the association of histones with DNA is stronger…?
the DNA-histone complex is More condensed (tightly packed). DNA is not accessible by transcriptional factors, which therefore can not initiate production of mRNA, so the gene is witched off
doing what to the complex inhibits transcription and How is this brought about?
Condensation of the DNA-histone complex inhibits transcription. it can be brought about by decreased acetylation of the histones or by methylation of DNA
Decreased Acetylation of associated Histones
What is acetylation?
Acetylation is the process whereby an acetyl group is transferred to a molecule. In this case the group donating the acetyl group is Acetylcoenzyme A (from link reaction)
What is Deacetylation?
is the reverse reaction where an acetyl group is removed from the molecule
Explain how decreased Acetylation of Associated Histones affects gene expression?
- decreased acetylation increases the positive charge on histones and therefore increased their attraction to the phosphate groups of DNA.
- The association between the DNA and histones is stronger and the DNA is not accessible to transcriptional factors
- these transcriptional factors can not initiate mRNA production from DNA
- the gene is therefore switched off
Increased Methylation of DNA
what is methylation?
methylation is the addition of a methyl group to a molecule. in this case the methyl group is added to the cytosine bases of DNA.
Methylation inhibits transcription in two ways?
- preventing the binding of transcriptional factors to the DNA
- attracting proteins that condense the DNA-histone complex (by inducing deacetylation of the histones) making DNA inaccessible to transcriptional factors
Draw out the Epigenetics table on the Epigenetics sheet
Epigenetics on inheritance and treating disease
How is epigenetics inherited?
organisms inherit their DNA base sequence from their parents. Most Epigenetics marks on the DNA are removed between generations, but some escape the removal process and are passed onto offspring . This means that the expression of some genes in the offspring can be affected by environmental changes that affected their parents or grandparents
Give an example?
in humans, when a mother has a condition known as gestational diabetes, the fetus is exposed to high concentrations of glucose. Which can cause epigenetic changes in the daughter’s DNA, increasing the likelihood that she will develop gestational diabetes herself.
How has the link between epigenetics and inheritance investigated?
- investigations on mice
- twin studies
Can Epigenetic changes be reversible?
Epigenetic changes are reversible
What can epigenetic changes cause? How?
Certain diseases. By altering any of the epigenetic processes can cause Abnormal activation or silencing of genes. Such alterations have been associated with a number of diseases such as Cancer
Describe how cancer can be caused by two types of genes?
- the activation of a normally inactive gene can cause cancer
- the inactivation of a normally active gene, can cause cancer
How did researchers find out that Cancer was caused by Epigenetic changes?
researchers found that diseased tissue taken from patients with cancer has less DNA methylation than normal tissue from the same patients. increased DNA methylation normally inhibits transcription (switches off gene). This means that these patients with less DNA methylation would have higher gene activity - more genes turned on
But why can increased methylation still cause certain cancer?
some specific sections of DNA have no methylation in normal cells. However in cancer cells these regions become highly methylated CAUSING GENES THAT SHOULD BE ACTIVE TO SWITCH OFF. As a result, damaged base sequences in DNA are not repaired and so can lead to cancer.
Why are Epigenetic changes are a lot easier to treat than DNA sequence mutations?
Epigenetic changes are a lot easier to treat than DNA sequence mutations due to their reversibility.
What do drugs help to do?
Drugs are designed to counteract the epigenetic changes that cause the disease.
Which two processes do drugs inhibit?
Drugs can inhibit certain enzymes involved in either histone acetylation or DNA methylation.
E.g. drugs that inhibit enzymes that cause DNA methylation can reactivate genes that have been silenced.
Why does Epigenetic therapy need to be specifically targeted to Cancer cells?
If drugs were to affect normal cells they could activate gene transcription and make them cancerous, so causing the very disorder they were designed to cure.
What is another use of epigenetics in the treatment of disease
- development of diagnostic tests that help detect the early stages of diseases such as cancer, brain disorders and arthritis
- these tests can help identify the level of DNA methylation and Histone Acetylation at an early stage of disease
- this allows those with these diseases to seek early treatment and so have a better chance of cure
The Effect of RNA interference on Gene expression
This process occurs in both..?
Prokaryotes and eukaryotes
Which process can be inhibited in both prokaryotes and Eukaryotes?
In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi).
What is RNA interference (RNAi)?
This is when mRNA that has already been transcribed get’s destroyed before it is translated to create a polypeptide chain (turns off gene)
OR
Breaking down mRNA before it’s coded information can be translated into a polypeptide
OR
where small, double stranded RNA molecules stop mRNA from target genes being translated into proteins
What is the small molecule involved in this reaction called?
Small interfering RNA (siRNA)
When is double-stranded RNA made?
- Double stranded RNA is made when there is lot’s of one type of mRNA floating in the cytoplasm
- This results in
How is double-stranded mRNA made?
- There is a high concentration of one type of mRNA in the cytoplasm
- this results in RNA dependent RNA polymerase producing Double stranded RNA by using mRNA as a template
- to produce a complimentary RNA strand
- Two RNA strands join together forming Hydrogen bonds
How is siRNA made?
- Double stranded RNA is cut into smaller sections of RNA by an enzyme called Dicer
- These small sections of RNA are called small interfering RNA
What are some of the properties of siRNA?
- usually 21-23 base pairs long
- two bases overhand at each of siRNA
Describe how siRNA turns off genes?
- siRNA combines with a protein complex RISC , forming a siRNA-RISC complex
- This separates the two separate strands of siRNA, one of them is discarded/destroyed.
- The other strand (siRNA-complex) is complimentary to the mRNA and binds to the mRNA (complimentary base pairing)
- This attachment inactivates the mRNA, the protein (RISC) will cut the mRNA into smaller fragments/sections (the mRNA has been cleaved and degraded by the cell)
- The mRNA is no longer capable of being translated into a polypeptide
- the gene has not been expressed (it has been blocked)
What does RISC stand for?
RNA induced silencing complex
What is the importance of siRNA in research?
by turning of a gene and observing its consequences, it allows better understanding as to what the gene does.
What is the importance of siRNA in Medicine?
They can turn off genes associated with a particular disease. OR if a disease is caused by the activity of a gene could be targeted with siRNA e.g. Cancer, autoimmune diseases, .viral infections or dominant genetic diseases.
What is believed to be the natural function of siRNA?
Destroys viruses which naturally have Double stranded RNA (dsRNA)
Gene Expression On Cancer
What is Cancer?
Cancer is a result of mutation in genes that regulate Mitosis and the cell cycle, leading to uncontrolled cell growth
Because mitosis is not regulated (non-functioning proteins made), it leads to a formation of a..?
Tumour, which is a mass/group of abnormal cells
Tumours that invade and destroy surrounding tissues are called?
Cancers - However, not all Tumours are cancerous?
What are the two types of tumours?
Benign and Malignant tumours
What are Benign Tumours?
Benign tumours are not cancerous. They usually grow slower than malignant tumours and are often covered in fibrous tissue that stops cells invading other tissues. Benign tumours are often harmless, but they can cause blockages and put pressure on vital organs. Some benign tumours can become malignant.
What are Malignant Tumours?
Malignant tumours are cancerous mass of undifferentiated cells. They usually grow rapidly and invade and destroy surrounding tissue. Cells can break off the tumour and spread to other parts of the body.
Compare Benign Tumours (table in textbook)
1) Size and Growth
2) appearance of nucleus
3) nature of cells
4) spread)
5) capsule or no capsule?
6) life-threatening?
7) localised or systematic?
8) method of removal?
9) reoccurrence?
1) Grow very large and slowly
2) the cell nucleus has a relatively normal appearance
3) cells are often well differentiated
4) Cells produce adhesion molecules that make them stick together and so they remain within the tissue from which they arise (primary tumours)
5) Tumours are surrounded by a capsule of dense tissue so remain as a compact structure
6) much less life-threatening but they can disrupt functioning of vital organs
7) tend to have localised effects on the body
8) can usually be removed by surgery alone
9) rarely occur after treatment
Compare Malignant Tumours (table in textbook)
1) Size and Growth
2) appearance of nucleus
3) nature of cells
4) spread)
5) capsule or no capsule?
6) life-threatening?
7) localised or systematic?
8) method of removal?
9) reoccurrence?
1) Grow very large and rapidly
2) the cell nucleus if often larger and appears darker due to abundance of DNA
3) cells are undifferentiated
4) Cells do not produce adhesion molecules so they tend to spread to other regions of the body, via a process called metastasis, forming secondary tumours
5) Tumours are not surrounded by a capsule of dense tissue and so can grow finger like projections into the surrounding tissue
6) more likely to be life-threatening as abnormal tissue replaces normal tissue
7) Often have systematic effects (whole body) such as weight loss and fatigue
8) usually be removed by surgery along with radiotherapy and chemotherapy
9) frequently reoccurs after surgery
What is Metastasis?
meaning that the tumour can break off and spreads to other parts of the body
Why do cells go through cell division/mitosis?
Cells divide to ensure that dead or
damaged cells are replaced.
What does DNA analysis of Cancer show??
Shown that in general cancer cells are derived from a single mutant gene. The initial mutation leads to uncontrolled mitosis. A further mutation leads to changes to cells to be different from normal cells in both growth and appearance
what are the Three main causes of tumour development?
- Due to a gene mutation in a tumour suppressor genes and or oncogenes
- abnormal methylation of tumour suppressor genes and oncogenes
- increased oestrogen concentrations in the
development of some breast cancers.
The rate of cell division is controlled by what two genes?
- Tumour suppressor genes
- Proto-oncogenes
What are Proto-Oncogenes?
Proto-oncogenes codes for a protein involved in the initiation of DNA replication and Mitosis (cell division) , when the body needs new cells. So stimulates cell division
What is an Oncogenes and how does it lead to the formation of a tumour ?
Oncogenes are mutated Proto-oncogenes, Oncogenes can result in the a permanently activated gene. This stimulates cells to divide uncontrollably resulting in a tumour.
Describe two ways in which a oncogene can be permanently activated?
- the receptor protein on the cell-surface membrane can be permanently activated, so cell division is switched on even in the absence of growth factors
- the oncogene may code for a growth factor that is then produced in excessive amounts, again stimulating excessive cell division.
Most mutations in oncogenes are are..?
acquired and not inherited
(an acquired gene mutation is not inherited from a parent. Instead, it develops at some point during a person’s life.)
What are Tumour Suppressor genes?
these genes produce proteins that slow down cell division and cause cell death if DNA copying errors are detected (apoptosis) and therefore maintains the normal rates of cell division and prevents the formation of tumours
Describe what happens in a mutated Tumour suppressor genes, and how it leads to the formation of a tumour?
if a mutation occurs in a tumour suppressor gene, the gene will become inactivated. The protein it codes for (that inhibits cell division) isn’t produced and so the cells divide uncontrollably, the rate of cell division increases, resulting in a tumour
What is the important difference between Oncogenes and Tumour suppressor genes?
oncogenes cause cancer as a result of activation of Proto-oncogenes While Tumour suppressor genes cause cancer when they are inactivated
Which two forms of the Tumour suppressor gene causes breast cancer?
BRCA1 AND BRCA2 (increased Methylation)
These can be caused by..?
Inherited mutations
Why is Methylation important?
it can control whether or not a gene is transcribed and translated into a protein
Explain How abnormal methylation of Tumour suppressor genes can cause cancer?
- Hypermethylation occurs in a specific region of tumour suppressor genes (promoter region)
- as a result, transcription of the tumour suppressor gene is inhibited
- The gene is inactivated and becomes witched off
- Proteins that needed to slow down/ turn off mitosis are not being produced
- This means that cells are able to divide uncontrollably by mitosis, leading to the formation of a tumour
Explain How Abnormal Methylation in Oncogenes leads to the formation of cancer/ tumour?
- Hypomethylation occurs in a specific region of Oncogenes (promoter region)
- as a result, transcription of the Oncogene is increased
- The gene is permanently activated and becomes switched on
- MORE Proteins that stimulate mitosis are produced
- This means that cells are divide uncontrollably by mitosis constantly, leading to the formation of a tumour
What is the role of Oestrogen normally?
Oestrogen is produced by the ovaries to regulate the menstrual cycle, But after menopause, oestrogen production stops
What is thought to increase a women’s risk of breast cancer after menopause?
High oestrogen concentrations in fast cells of breast tissue
Why is this?
When menopause begins, oestrogen begins to be produced in the fat cells of breast tissue and thus is believed to be the cause of post-menopause cancer
Why is Oestrogen believed to cause breast cancer?
- This is because Oestrogen is able to activate a gene by binding to a gene which promotes transcription.
- If a gene that Oestrogen acts on is one that controls cell division and growth, then it will be activated and it’s continued division could produce a tumour
Describe a process by which oestrogen may cause breast cancer in post-menopausal women?
- fat cells of the breast tend to produce more oestrogen after menopause
- these locally produced oestrogens release an inhibitor molecule that prevents transcription causing proto-oncogenes of breast tissue to develop into oncogenes.
- these oncogenes increase the rate of cell division leading to the development of a tumour (breast cancer)
Explain How oestrogen leads to the growth of a tumour cell?
Once a tumour has developed, it further increases oestrogen concentrations which therefore leads to a increased development of the tumour. It also appears that white blood cells that are drawn to the tumour increase oestrogen production. This leads to an even greater development of the tumour
Describe three other theories, as to how Oestrogen causes breast cancer to arise?
- oestrogen can stimulate certain breast cells to divide and replicate. The fact that more cell divisions are taking place naturally increases the chance of mutations occurring , and so increases the chance of cells becoming cancerous
- Oestrogen’s ability to stimulate division could also mean that if cells do become cancerous, their rapid replication could be further assisted by oestrogen, helping tumours to form quicky
- other research suggests that oestrogen is actually able to introduce mutations directly into the DNA of certain breast cells, again increasing the chance of these cells becoming cancerous
what are the risk factors for Cancer?
there are both genetic and environmental risk factors for cancer
What are examples?
Genetics - inheriting an allele
Environmental - tobacco smoking, alcohol, carcinogens, Highly ionising radiation
How can we prevent cancer?
is a specific cancer causing mutation is known, then it is possible to screen for the mutation in the person’s DNA Knowing about this increased risk means that preventative steps can be taken to reduce it.
Knowing about specific mutations causing cancer, we can?
develop more sensitive tests which can lead to more accurate and earlier diagnoses
How can cancer caused by mutated cells be possibly treated?
Gene therapy - where faulty alleles in a persons cells are replaced by working versions of those cells
FINISHED
