MUTATION & MUTAGENESIS Flashcards
What about point mutations?
They are the most common and the least dangerous
Most dangerous mutations
Addition or deletion
What are pyrimidines?
C/T/U
What are purines?
A/G
3 main causes of mutations
1) DNA damage
2) random insertion of transposable elements
3) Replication errors
Describe a transition point mutation
The mutation of a pyrimidine to a pyrimidine or a purine to a purine
Describe a transversion point mutation
The mutation of a purine to a pyrimidine or pyrimidine to a purine
What is a tautomer?
What kind of mutation do they cause?
An alternative form of a nucleotide base that bonds to a different base from its usual complement
- Can cause a point mutation.
Thymine is normal in its __(a)__ form. Its tautomer is called the __(b)___ form and has a double bonded ___(c)___. This means that it binds to ___(d)____ as opposed to ___(e)____.
a) keto
b) enol
c) Nitrogen
d) guanine
e) adenine
Cytosine is normal in its ___(a)___ form. Its tautomer is called the ___(b)__ form and binds to ___(c)___ instead of ___(d)____.
a) amino
b) imino
c) adenine
d) guanine
3 ways in which errors in DNA replication can lead to mutation
1) failure of the epsilon subunit to correct mismatch when proof reading
2) tautomeric shift causing mismatches
3) replication slippage
a) How do replication slippages occur?
a) repeating bases such as ctctctct will bind to a corresponding sequence elsewhere creating a loop or slip
- DNA repair will often delete the loop and cause a frameshift
A slippage on the TEMPLATE strand can cause….
deletions
A slippage on the NEWLY SYNTHESISED STRAND can cause…
additions
EXTERNAL damage to DNA
a) How does UV radiation damage DNA?
b) How does ionising radiation damage DNA?
c) How do external chemicals such as cigarette smoke damage DNA?
a) cause pyrimidine dimers to be formed
b) breaks in DNA
c) can damage bases
Internal cellular damage attacks DNA ______
nucleotides
What is an abasic site?
is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage.
_____ can create abasic sites through hydrolysis of purine bases.
Depurination
What does deamination cause?
hydrolysis of amino group from cytosine & 5- methyl cytosine and cause mispairing of bases
how does oxidative damage affect DNA?
damage the rings of purine and pyrimidine bases
Key point of DNA mismatch system?
Which DNA polymerase does it use? Other enzymes?
recognises that the DNA helixes are distorted and cuts newly synthesised strand
DNA pol I
DNA ligase
BEP stands for?
Base excision repair
In the base excision repair system, which base is recognised as unnatural in DNA?
How might this have occurred?
uracil
deamination
How is uracil removed using the base excision repair system?
1) Abasic site formed as uracil is removed using DNA glycosylase
2) AP endonuclease cuts phosphodiester bonds
3) DNA pol I fills gap and DNA ligase seals
What form of DNA damage is the nucleotide excision repair system used to repair? How does it stall DNA polymerase?
Depurination, forming pyrimidine dimers
- the diners next to eachother form a covalent bond which means that DNA pol III cannot get past
How does the bacterial NER function?
PHOTOREACTIVATION
1) UvrAB scans and finds damafe
- UvrBC creates nicks at 5’ and 3’ end to the lesion
- UvrD is a helicase that releases damaged segment
-DNA pol I fills the gap and ligase seals
What are DNA polymerases IV and V used for ?
(TRANSLESION DNA SYNTHESIS)
when DNA damage is too great, NER is bypassed and these are used to bypass the dimer BUT very error prone
Describe 6 ways that we can artificially induce mutation
1) introduce transposons
2) base analogues that tautomerise more frequently are introduced
3) EMS
4) proflavin for framsehift mutations
5) Alfatoxin B
6) bisulphite
