Causes of mutations Flashcards
What are the 2 type of mutations?
- Single base change mutations = point mutations e.g. silent, missense, nonsense, framshift mutations (insertions + deletions)
- Large chromosomal rearrangements e.g. duplication, insertion, deletion, inversion, translocation
Expand on the outcome of the different kinds of single base change mutations:
- SILENT
- MISSENSE
- NONSENSE
- FRAMESHIFT INSERTION
- FRAMESHIFT DELETION
- no change in amino acid sequence of polypeptide
- slightly different amino acid sequence
- polypeptide synthesis ceased
- major difference in amino acid sequence
- major difference in amino acid sequence
What are epigenetic mutations?
Changes in the DNA that don’t involve the base sequence e.g. chemical modification of the DNA e.g methylation of cytosine bases. These control whether genes are expressed.
What can be the effect of mutations in terms of function?
What are conditional mutations?
Some mutations may cause loss of function, some may cause gain of function (can be harmful).
They exhibit their effect only under specific conditions.
Difference between somatic v.s germ-line and acquired v.s. inherited?
Some mutations in cancers are inherited. These germ-line (present in egg or sperm) mutations would be present in every cell of a person’s body.
MOST mutations are acquired during the person’s lifetime as somatic mutation (occur in non germ-line tissues). These are present only in the tissue in which they originate and are NOT inherited.
Heritable cancer risk. Most cancers are said to be ______. The rest are familial and ______.
sporadic
inherited
Penetrance is
the extent to which somebody with a gene mutation shows the predicted phenotype.
Somatic mutations are acquired during a person’s life time in two main ways:
- spontaneous mutations (arise from errors in DNA replication)
- induced mutations (result of extrinsic DNA damage. Most damage is repaired efficiently but mutations arise from inaccurate repair)
Spontaneous mutations occur when there is an error in DNA replication. What are some processes that work to allow cellular genomes to be copied in high fidelity manner at very cell division cycle?
- faithful DNA replication
- DNA proof-reading
- Mismatch repair
Outline DNA proof-reading
DNA replication is carried out by DNA polymerases with proof reading function.
They synthesis DNA from 5’ to 3’ and the back-track to proofread from 3’ to 5’.
Incorrectly incorporated nucleotides are thus removed.
What does mismatch repair (MMR) do?
What is recognised for repair?
It corrects those errors missed by proof-reading shortly after DNA synthesis.
Mismatches are recognised as distortion of DNA geometry.
MMR proteins cut out ONLY the newly synthesised strand, which can then be repaired.
Induced mutations arise through the cell’s attempt to repair DNA damage induced by:
Intrinsic factors - oxidative damage - hydrolytic damage Extrinsic factors - radiation (UV) - viruses - alkylation (addition of methly or ethyl to DNA bases)
INTRINSIC FACTORS:
Hydrolytic DNA damage can occur through de_______ (loss of NH2 groups) and de________ (loss of entire bases)
deamination (loss of NH2 groups)
depurination (loss of entire bases)
EXTRINSIC FACTORS:
- UV light induces the formation of pyrimidine dimers in which two adjacent _____ (e.g thymines) are joined by a cyclobutane ring structure)
- many carcinogens react with DNA bases, resulting in the addition of large bulky c____ groups to the DNA molecule,
- pyramidine
- chemical. Benzo(a)pyrene epoxide reacts specifically with guanine bases.
Mutagens e.g. benzo(a)pyrene - ( a carcinogen found in tar/coal) is activated by _____ metabolism. It is the e__ide form that reacts with DNA (guanine bases)
CYP450/ liver
epoxide
