13.7 Mutations, Gene Expression and Cancer Flashcards
What are the 3 types of genetic code?
Universal, non-overlapping and degenerate
Define universal code
The same 3 bases on mRNA (codon)/DNA (triplet) code for the same amino acid in all organisms.
Define non-overlapping code
The ribosome reads each base only once in the codons/triplets- the first three bases are read first, followed by the second three, the third three and so on.
Define degenerate code
More than one triplet/codon codes for an amino acid
3 bases on DNA
Triplet
3 bases on mRNA
Codon
3 bases on tRNA
Anticodon
Define mutation
A mutation is a change to the DNA base sequence.
Define gene mutation
AKA single-point mutation.
Change to a single base in DNA base sequence of a gene.
Occurs randomly and happen spontaneously.
What may a mutation lead to?
Change in primary stucture of polypeptides, altering secondary structure, altering tertiary structure, making protein non-functional
Types of gene mutation
Addition, substitution, deletion
What is a silent mutation?
One where the mutation does not change the amino acid coded for so will have no effect on the polypeptide chain.
What is a frame shift?
When one full DNA nucleotide is gained or lost through addition or deletion mutations, this results in an altercation of base triplets from the mutation onwards. The reading frame will have been shifted either left or right.
Effect of timing of addition or deletion mutation
The earlier addition or deletion occurs, the more triplets that could be affected and so more AAs altered.
Define chromosome non-disjunction
Where daughter cells are produced containing too many chromosomes.
Pair of homologous chromosomes may fail to separate during metaphase 1 OR sister chromatids may fail to separate in metaphase 2.
Types of chromosomal mutations
Inversion, duplication, translocation
What is an inversion mutation?
When a segment of bases or a chromosome is reversed end to end.
What is a duplication mutation?
A doubling of part of a chromosome, an entire chromosome, or even the whole genome.
What is a translocation mutation?
When groups of base pairs relocate from one area of the genome to another. This usually is between non-homologous chromosomes.
Examples of mutagenic agents
- High energy ionising radiation (e.g. X rays, gamma rays, alpha and beta particles, ultra violet)
- DNA reactive chemicals (e.g. benzene, bromine, hydrogen peroxide)
- Biological agents (e.g. some viruses and bacteria)
What is a totipotent cell?
Can divide (by mitosis) and produce any type of body cell.
Only translate part of their DNA to produce specific proteins, leading to cell specialisation
Found in zygote and early embryo (up to 8 cell stage)
What does gene expression require?
Transcription and translation
What is a pluripotent cell?
Can divide by mitosis but also begin to differentiate into the majority of specialised cells that make up tissues in the fetus.
Only translate part of their DNA.
Found in embryo and fetal stem cells.
What is a multipotent cell?
Retain the ability to differentiate into some different cell types.
Found in mature mammals (in tissues).
e.g. cells in the bone marrow that differentiate into RBC and WBC
What is a unipotent cell?
Capable of giving rise to only one cell type.
Found in mature mammals
e.g. cells in the heart differentiate into cardiomyocytes.
What are multipotent and unipotent stem cells vital for?
Growth and repair of damaged tissues.
How are stem cells used in medical research?
- Produce tissues for skin grafts.
- Research into producing organs for transplant.
- Research into how cells become specialised.
- Research into cancer and other serious diseases.
- Use of stem cells to cure diseases like Parkisons
What is a danger when using stem cells?
May divide out of control, leading to a tumour.
Ethical concerns when using stem cells
People consider that:
- It isnt right to use stem cells from embryos as embryos have human status from the moment of conception.
- Embryos could be potential human beings, but at early stages it is not a true human being and the removal of cells from spare embryos for medicine has benefits.
- Embryos have no moral rights whatsoever.
- Animals must be used in experiments before stem cells can be trialled on humans
What is a promoter region?
One or more base sequences found upstream of a gene that control expression of the gene.
What is a transcription factor?
Proteins that, when activated, bind to promoter region of a gene to stimulate RNA polymerase to begin transcription of the target gene.
Describe the mechanism by which a signal protein causes the synthesis of mRNA.
- signal protein {binds to / joins to / interacts with / activates}
- receptor on surface membrane;
- messenger molecule moves from cytoplasm and enters nucleus;
- {produces / activates} transcription factor;
- binds to promoter region;
- RNA polymerase transcribes target gene;
Explain how oestrogen enables RNA polymerase to transcribe its target gene.
- Oestrogen (lipid soluble hormone) diffuses through the cell membrane through the phospholipid bilayer;
- attaches to complementary ERα receptor;
- ERα receptor changes tertiary structure/shape;
- ERα receptor leaves protein complex which inhibited it’s action;
- oestrogen receptor binds to promoter region;
- enables RNA polymerase to transcribe target gene.
Why does RNA interference occur?
-Protein synthesis uses large amounts of ATP
-Overproduction of a specific protein is a waste of valuable ATP
-If a cell has synthesised enough of a specific protein
Two types of interfering RNA
microRNA (miRNA)
small interfering RNA (siRNA)
How does interfering RNA work?
- miRNA or siRNA binds to protein in the cytoplasm to form a RISC complex (RNA-induced silencing complex)
- miRNA/ siRNA has a complementary base sequence to part of a specific mRNA molecule.
- RISC inhibits gene expression by binding to complementary mRNA, causing either:
1. mRNA to be hydrolysed by an enzyme- RNA hydrolase.
2. Inhibition of initiation of ribosomal translation so ribosome cant attach to mRNA
What are epigenetics?
Involves inheritable changes in gene expression without changes to DNA base sequences.
How do inheritable changes (epigenetics) inhibit translation?
Increased methylation of DNA
Decreased acetylation of histones
Explain the process of methylation of DNA
Methyl group attached to CG bases on the promoter region upstream of the gene.
Catalysed by methyltransferase enzyme.
Explain the process of acetylation of histones.
Acetyl groups attached to tails of histone molecules.
Results in them becoming loosely packed, less condensed.
Promoter region exposed so transcription factors can bind, so RNA polymerase can bind so target gene can be transcribed.
What is a malignant tumour?
Fast growing, non-capsulated, do metastasise (spread)
What is a benign tumour?
Slow growing, capsulated, do not metastasise (spread)
What do proto-onco genes do?
Stimulate cell division
What do tumour suppressor genes do?
Inhibit 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 / causes cell death / apoptosis;
- No control of mitosis.
Describe how alterations to tumour suppressor genes can lead to the development of tumours.
- (Increased) methylation (of tumour suppressor genes);
- Mutation (in tumour suppressor genes);
- Tumour suppressor genes are not transcribed/expressed
- OR
- Amino acid sequence/primary/ tertiary structure altered;
- (Results in) rapid/uncontrollable cell division;
Describe how altered DNA may lead to cancer.
- (DNA altered by) mutation;
- (mutation) changes base sequence;
- of gene controlling cell growth / oncogene / that monitors cell division;
- of tumour suppressor gene;
- change protein structure / non-functional protein / protein not formed;
- (tumour suppressor genes) produce proteins that inhibit cell division;
- mitosis;
- uncontrolled / rapid / abnormal (cell division);
- malignant tumour;
