control of gene expression Flashcards
mutation
any change to the quantity or structure of DNA
gene mutation
any change to one or more nucleotide base, or any rearrangement of the bases
inversion of bases
a group of bases becomes separated from the DNA sequence and rejoins at the same position but in reverse order
translocation of bases
a group of bases becomes separated from the DNA sequence on one chromosome and becomes inserted into the DNA sequence of another chromosome
what is a spontaneous gene mutation
a permanent change that arises during DNA replication and occurs without any outside influences.
ionising radiation
Xrays
Alpha / Beta / gamma rays
non ionising radiation
UV light
this is absorbed by the nitrogenous bases and has various effects including Thymine Dimers being produced. This is where adjacent Thymine bases in one DNA strand couple together instead of with the complimentary Addenine on the other strand.
totipotent cells
cells that can mature into any body cell. This is the zygote and the first few divisions by an egg cell. Human embryonic stem cells.
pluripotent cells
found in embryos and can differentiate into cells derived from any of the three germ layers.
eg. embryonic stem cells
fetal stem cells
multipotent
these stem cells can produce only cells of a closely related family of cells eg. adult stem cells and. umbilical chord blood stem cells.
unipotent cells
can only differentiate into one type of cell. Their ability for self renewal however makes them therapeutic in treating diseases (eg. skin transplants for burn victims).
induced pluripotent stem cells (iPS cells)
can be produced by adult somatic cells (in the lab) using appropriate protein transcription factors. The fact that these cells are capable of being reactivated shows that adult cells retain the same genetic information that was present in the embryo.
Although iPS cells express many of the same genes as embryonic stem cells, they are not exact duplicates of them. However, one feature that they do have is of self renewal, meaning they can potentially indefinitely multiply and therefore provide a limitless supply, so could replace the use of embryonic stem cells in medical research thus overcoming many of the ethical issues surrounding the use of embryos .
epigenetic
the heritable changes to gene expression in eukaryotic cells. (ie. genes can be switched on to off, and this on or off setting can be passed on when that cell divides).
Epigenetic changes are heritable but also reversible. So that genes that have been switched off can be switched back on again.
Epigenetic changes effect the phenotype of the cell without changing the underlying genotype of the DNA (so the DNA base sequence is unaffected).
epigenome
the collective name for the chemical tags attached to DNA and histones.
transcription factor
a protein that binds to a specific DNA sequence, thereby controlling the rate of transcription of genetic information from DNA to mRNA. They contain one or more DNA binding domains which attach to specific sequences of DNA adjacent to the genes that they regulate (they attach to promotor regions).
promotor region
a sequence of about 100 genes upstream (before) the gene. This is where activated transcription factors bind to allowing RNA polymerase to initiate transcription.
How does the Oetrogen steroid hormone work
- Is lipid soluble and therefore easily diffuses through the phospholipid bilayer into the cytoplasm of the cell.
- It binds to a complimentary receptor molecule on the transcription factor.
- this causes a tertiary structure change that means the DNA binding site on this transcription molecule changes shape, and is now complimentary to DNA.
- The transcription factor enters through the nuclear pore and binds to a specific base sequence on the DNA.
- This stimulates transcription of the gene
what is the name of the main drug used to treat breast cancers which are oestrogen dependent tumours
tamoxifen. This drug is effective because ti has a similar shape to oestrogen. Therefore it can permanently bind to oestrogen receptors in the tumour cells, and blocks oestrogen itself from binding to them, and therefore prevents transcription and cell division.
name a drug that could be used for a non-oestrogen dependent tumour
Herceptin (the monoclonal antibody)
active genes
these are more accessible to transcription factors because the DNA is not so tightly coiled around the histone proteins
inactive genes
these genes are less accessible to transcription factor because the DNA is tightly coiled around the histones
imprinted genes
genes that do not have epigenetic markers removed after fertilisation.
methylation
when a methyl group is added to DNA. This methyl group prevents transcription. Opposite is DNA de-methylation which removes the methyl groups so allowing more transcription to occur.
what is methylation controlled by
a group of enzymes called DNA methyltransferases (DNMT’s).
acetylation
histone molecules contain the amino acid lysin. Acetyl groups (COCH3) may be added to these lysine residues, replacing one of their hydrogen ions. By removing the positively charged hydrogen ion, this causes the proteins to become lass wrapped around the DNA as theres less attraction.
AcetylCoA (same as in Krebs) adds the Acetyl group.
heterochromatin
tightly packed chromatin (= gene switched off)
euchromatin
loosely coiled chromatin (= gene switched on)
effect of DNA hypomethylation
to little methylation can activate oncogenes
effect of DNA hypermethylation
can silence / inactivate tumour suppressor genes
what is siRNA
short interfering RNA
RNA interface and how it prevents translation
- DS RNA is produced in the nucleus when the concentration of mRNA becomes too high
- the dsRNA is cut into very short lengths of siRNA by an enzyme.
- a protein in the cytoplasm then separates out the two strands. one of the strands is then removed by degradation by enzymes.
- the other strains then binds to an enzyme and guides the enzyme to an mRNA molecule.
- once in position, the enzyme cuts the mRNA into smaller sections meaning that the mRNA is no longer capable of being translated into a polypeptide and so the gene is not expressed.
repairing mutations
nucleotide excision repair:
- damage is cut out (excised) by an endonuclease enzyme
- the missing sequence is then repaired by DNA polymerase
- This is then sealed by Ligase enzyme
tumour suppressor genes
produce proteins that…
- slow down cell division
- repair mistakes in the DNA
- destroys cells by apoptosis if the mistakes in the DNA are beyond compare
they are generally recessive.
3 examples of tumour suppressor genes
TP53
BRACA1
BRACA2
what does the TP53 gene do
codes for the p53 proteins. This protein is involved in the process where if DNA is damaged beyond repair it triggers apoptosis.
proto oncogenes
normal proto-oncogenes code for G proteins. These enable cells to respond to growth factors which cause cells to divide. They are inactivated by their own enzyme GTPase
what happens when a mutation turns a protoctist-oncogene into an oncogene
it produces G proteins that are deficient in GTPase. This means that the G proteins are active for longer and therefore there is uncontrolled cell growth. This is dominant.
effects of the chemical mutagen nitrogen dioxide
e.g.. Nitrogen dioxide can directly alter the structure of DNA or interfere with transcription.
effects of the chemical mutagen tobacco
Benzopyrene is a constituent of tobacco sample that inactivates the tumour suppressor gene TP53 leading to cancer.
effects of the chemical mutagen mustard gas
mustard gas adds an alkyl group to guanine, which triggers the guanine to be released and therefore a space is left to be replaced by another base.
chemical mutagens and examples
- nitrogen dioxide
- tobacco
- caffeine
- some pesticides
some chemical mutagens have a structure to the bases and therefore can be placed in the DNA molecule in place of a real base.
