regulation of the gene expression Flashcards

1
Q

recap of protien synthesis

A

-transcription of the gene in the nucleus using RNA polymerase to convert DNA to RNA - free nucleotides allign due to comp base pairing
-pre-mRNA spliced and introns removed
-mRNA leaves nucleus via nuclear pore
-mRNA binds to ribsome on RER
-translation of the mRNA into a polypeptide
-modification, folding and packaging of the protein in the golgi

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2
Q

how do cells become differentiated

A

when a gene is expressed or witched on and transcribed to mRNA and then translated to a protien

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3
Q

what are transcription factors

A

regulatory proteins that stimulate a gene

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4
Q

how do transcription factors work

A

the control the rate of transcription by either activating or repressing RNA polymerase
-each factor binds to a specfic region of DNA before the gene

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5
Q

what is the promoter region

A

region before the gene that is the binding site of RNA polymerase and is therefore the starting point of the transciption of that gene

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6
Q

what do repressors do

A

bind to the promoter region and prevent the RNA polymerase from binding and stopping the gene

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7
Q

what can transcription factors be switched off by

A

an inhibitor molecule

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8
Q

what is the role of an inhibitor molecule

A

binds to the transcriptional factor which prevent it from attaching to the promoter region
-without the factor the gene may not be transcribed (if the TF is an activator) or the gene may not be expressed ( if the TF is a repressor)

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9
Q

what is an example of a transcriptional factor

A

oestrogen

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10
Q

what is oestrogen

A

a steroid hormone found in mammals and is involved in controlling the female fertility cycle and sperm production in males

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11
Q

what is a steroid hormone

A

small, hydrophobic,lipid-based hormone that can diffuse through the cell membrane and can pass directly into the nucleus through a nuclear pore

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12
Q

describe the oestrogen stimulation pathway

A

-Oestrogen diffuses through the cell surface membrane into the cytoplasm
-Oestrogen diffuses through a nuclear pore into the nucleus
-Within the nucleus, oestrogen attaches to an ERα oestrogen receptor that is held within a protein complex, this causes the ERα oestrogen receptor to undergo a conformational change
-The new shape of the ERα oestrogen receptor allows it to detach from the protein complex and diffuse towards the gene to be expressed
-The ERα oestrogen receptor binds to a cofactor which enables it to bind to the promoter region of the gene, this stimulates RNA polymerase binding and gene transcription

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13
Q

what are RNAi molecules

A

small lengths of non-coding RNA which regulate the gene expression by affecting translation instead of transcription

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14
Q

how are RNAi different do RNA and what effect to they have on mRNA

A

-double-stranded
-stop mRNA that has been transcribed already from being translated into a protien

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15
Q

what are the two types of RNAi

A

short interfering RNA (siRNA) in animals
micro RNA (miRNA) in plants

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16
Q

how does siRNA and miRNA work - in plants

A

-double stranded siRNA associates with proteins in the cytoplasm and unwinds
-one of the siRNA strands is chosen and the other degrades
-single strand of siRNA binds to the target mRNA - as is comp to base sequence
-proteins are turned into small fragments so can no longer be translated
-mRNA fragments then move into a processing body which degrades them

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17
Q

how does miRNA work in animals

A

-not fully comp to target mRNA so they are often less specific an can target more than one mRNA molecule
miRNA has to go through the processing stages in the cytoplasm to get to be a single strand like siRNA
from a folded strand to a double strand then two single strands then one of these is degraded as with siRNA

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18
Q

how does miRNA work on the ribosome when it is a single strand

A

once the miRNA is bound to the mRNA it does not cause degradation instead it simply blocks the translation by preventing the ribosome from binding
the mRNA is then move into a processing body where it can be stored - to be returned and translated another time or to be degraded

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19
Q

why might mammalian miRNA target a greater range of mRNA than siRNA

A

not fully comp to base sequence so less specific than siRNA

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20
Q

How is control of the gene expression important in cancer

A

Rate if cell division is controlled by genes and if mutations occur in these genes then uncontrolled cell division will occur - leading to cancer

21
Q

What are the two types of cell that control cell division

A

Proto-oncogenes
Tumour suppressor genes

22
Q

What are proto-oncogenes

A

Stimulate cell to divide when growth factors attach to receptors on their surface - this activates genes and causes DNA to replicate

23
Q

What is an oncogene and how does it cause cancer

A

Mutated proto-oncogene that causes cancer
The protein receptor is permanently turned on even in the absence of mutation leading to cells continuously dividing

24
Q

What are tumour suppressor cells

A

Normally help cells slow down cell division, repair DNA mistakes or tell cells when to undergo apoptosis

25
How can tumour suppressor cells cause cancer
When they are activated or turned off - abnormal cell growth Eg TP53
26
What factors effect the rate of cell division
Environment = oxygen and nutrients Hormones = growth factors Genes Mutations
27
How can mutations cause cancer
Change to the sequence of bases on the DNA Caused by mutagenic agents or inherited mutations The mutations that result in the generation of cancerous cells do not result in early cell death or in the cell being destroyed by the body’s immune system This means that the harmful mutation occurring in the original cell can be passed on to all that cell’s descendants
28
Give an example of a hereditary cancer
Breast cancer caused by mutated BRCA-1 or 2 BRCA-1 is an example of a human tumour suppressor gene expressed mainly in breast tissue The role of the BRCA-1 protein is to repair broken or mutated DNA If the BRCA-1 protein cannot repair the DNA it signals for apoptosis to begin In breast cancers, inhibition of BRCA-1 expression leads to a lack of DNA repair and apoptosis, leading to the formation of cancerous tumours
29
What are the two types of tumour
Malignant Benign
30
How do tumours form
Abnormal cell growth that form lumps
31
How do tumours damage to the body
Damaging the organ in which the tumour is located Causing blockages or obstructions Damaging other organs by exerting pressure
32
What are malignant tumours
Malignant tumours are cancerous Malignant tumours cause cancer by growing rapidly, then invading and destroying surrounding tissues Cells within malignant tumours secret chemicals that cause the formation of blood vessels to supply the tumour with nutrients, growth factors and oxygen Cells can break off these tumours and spread to other parts of the body through the bloodstream or lymphatic system, this is called metastasis Metastasis causes the spread of tumours to other places in the body, affecting multiple organs When removed through surgery, malignant tumours can still grow back The formation of malignant tumours can be initiated by carcinogens such as: UV or X-ray exposure Tobacco from cigarettes Asbestos Processed meat
33
What are benign tumours
Benign tumours are not cancerous These tumours grow slowly Benign tumours do not invade other tissues and do not metastasise, unlike malignant tumours These tumours can cause damage such as blockages or by exerting pressure on the organ it is growing in or those surrounding it When removed, benign tumours do not usually grow back The formation of benign tumours can be initiated by: Inflammation or infection Injury Diet Genetics Toxins and radiation Examples of benign tumours are: Polyps found in the nose, colon and ovaries Non-cancerous brain tumours Warts, caused by a viral infection
34
How does oestrogen increase the risk of breast cancer
Oestrogen is a steroid hormone that upregulates transcription of certain genes through the stimulation of the ERα oestrogen receptor High concentrations can be a result of over-expression of the oestrogen gene or from supplementary oestrogen taken in medication About 70% of breast tumours are categorised as oestrogen receptor-positive, these breast tumours are also called oestrogen-dependent breast tumours Oestrogen is needed by these tumours to stimulate the expression of cell cycle genes that lead to growth and replication The cancer cells within these tumours have oestrogen receptors that promote cell growth when stimulated by oestrogen The genes are switched on through the oestrogen dependent gene expression pathway in which oestrogen diffuses into the cell and through a nuclear pore until it reaches the oestrogen receptors - stimulate breast tissues to divide
35
How is cancer treated
-surgery -Chemotherapy and radiotherapy are used, which specifically target and kill rapidly dividing cells.-stops S division as it can’t take place
36
What is epigenetics
heritable changes in gene function, without changes to the base sequence of DNA
37
What are histones
Associate to DNA and help dna condense to chromatin Covered in chemicals known as tags which determine the shape of the histone-dna complex and help to control transcription of the genes
38
What is the epigenome
All of the chemical modifications to all histone proteins and DNA (except base changes) in an organism is called the epigenome In eukaryotic cells, the DNA in the nucleus is wrapped around proteins called histones Histone proteins can be chemically modified through the addition of acetyl DNA can also be chemically modified through the addition of methyl groups without changing the base sequence which also leads to the regulation of gene expression
39
How can the epigenome undergo change
Changes to the epigenome are caused by changes in the environment Smoking, stress, exercise and diet can cause epigenetic changes Internal signalling from the body's own cells can also cause modifications to occur
40
How does the chemical modification control transcription factors
The chemical modification of histones and DNA controls how tightly the DNA is wound around them as the intermolecular bonding between the histones and DNA changes If the DNA is wound more tightly in a certain area, the genes on these section of DNA are 'switched off' as the gene and promoter regions are more hidden from transcription factors and RNA polymerase
41
What is acetylation of histones
Acetyl groups (COCH3) can be added to lysine amino acids on histone proteins Adding acetyl (acetylation) to lysine residues removes the positive ion and therefore removes a bond between the histone protein and the DNA, this causes the DNA to be less tightly wrapped When the DNA is less tightly wrapped, RNA polymerase and transcription factors can more easily bind and therefore gene expression is stimulated Removal of acetyl (deacetylation) returns lysine to its positively charged state which has a stronger attraction to the DNA molecule and therefore inhibits transcription
42
What is methylation of DNA
Methyl groups (CH3) can be added to a carbon molecule on cytosine bases within sequences that contain multiple cytosine and guanine bases The addition of methyl groups (methylation) suppresses the transcription of the affected gene This happens because the methylated bases attract proteins that bind to the DNA and inhibit transcription
43
How can methylation cause cancer
Hypermethylation -Methyl groups (could be) added to (both copies of) a tumour suppressor gene; -The transcription of tumour suppressor genes is inhibited; -Leading to uncontrolled cell division. RNA interference by siRNAs targeting tumour suppressor genes for breakdown can also lead to tumour development for the same reason Hypomethylation proto-oncogenes encourage cell division can stimulate cells to divide uncontrollably and form tumours
44
What is epigenetic imprinting
DNA methylation of certain genes and it occurs during the formation of oocytes and sperm cells
45
How does epigenetic imprinting cause disease
A child, therefore, inherits two sets of DNA, one from the mother and one from the father, each with its own epigenetic imprint Imprinting is reversible, therefore the maternal epigenetic imprints that are inherited by a male will become paternal imprints when his sperm are produced so that he passes on paternally imprinted DNA
46
What is prader-willi syndrome
example of a condition with epigenetic links The syndrome is caused by the silencing of an allele on chromosome 15 The severity of the syndrome depends on whether an individual receives the affected DNA from their mother or their father If the mother is a carrier for the defective chromosome, individuals that inherit the chromosome do not develop the syndrome However, if the defective chromosome is inherited from the father, the individual will develop the syndrome
47
How can epigenetics be used to treat cancer
DNA in human tumour cells have changes in DNA methylation and histone acetylation which causes tumour suppressor genes to be silenced and oncogenes to be activated This leads to deregulation of the cell cycle and the formation of tumours Some cancer treatments involve drugs that reverse the epigenetic changes through the removal of acetyl and methyl tags Removal of methyl groups from the DNA of tumour suppressor genes will enable the genes to be expressed The proteins produced can then regulate the cell cycle and stop tumours forming from faulty or cancerous cells Removal of acetyl groups from histone proteins attached to oncogenes causes the DNA to wrap more tightly, silencing these genes Reducing the expression of oncogenes stops cancer as faulty cells are able to die through programmed cell death (apoptosis) rather than continuing to replicate, causing cancer
48
What environmental factors affect epigenetics
-pollution -availability of food or drought -stress