Mod 8 - causes of DNA mutations + repair Flashcards
what is a mutation?
an alteration in the nucleotide sequence of the DNA molecule
what is a spontaneous mutation?
a mutation resulting from an error in DNA replication
- not common - most DNA polymerases have very good proofreading activities
what is a tautomer?
an isomer with a slightly different chemical structure
what are the 4 normal bases?
amino-adenine (pairs with T)
keto-thymine (pairs with A)
keto-guanine (pairs with C)
amino-cystosine (pairs with G)
what are the 4 less common tatuomers?
imino-adenine (pairs with C) - i ate cheese
enol-thymine (pairs with G) - elephant trunk goat
enol-guanine (pairs with T) - eat good toast
imino-cytosine (pairs with G) - ice cold goo
what is a mutagen?
a chemical or environmental agent that can cause changes in DNA molecules
what is a base analog?
a mutagen that can be incorporated into DNA but causes different base pairing and causes a mutation to occur
what is 5-bromouracil?
a base analog of thymine
- has a Br broup instead of a methyl group on thymine
what is the difference between keto-5bU and enol-5bU ?
- if keto-5bU is incorporated into replication instead of T, it binds to A - causes no change, is basically fine overall
- if enol-5bU is incorporated into replication, it binds to G - basically changes an A to a G (bad)
what is a deaminating agent?
- removes the amine group from a base
what happens when cytosine is deaminated?
gives uracil - pairs with A now
what happens when guanine is deaminated?
gives xanthine - blocks DNA replication
what happens when adenine is deaminated?
deamination of adenine gives hypoxanthine - doesn’t pair with T anymore - pairs with C now
what do alkylating agents do?
add alkyl groups e.g. ethylmethane sulphonate (EMS)
causes transition mutations
what do intercalating agents do?
inserts itself between base pairs (e.g. ethidium bromide)
causes insertion mutations
what does UV radiation do?
causes base dimerization
- attatches 2 bases together
how does heat mutate DNA?
- heat causes detatchment of bases - gives rise to an AP site
- AP = apurinic, apyrmidinic (depurination or depyrmidiation)
what are the 4 types of DNA repair?
- direct repair
- excision repair
- mismatch repair
- nonhomologous end-joining
what is direct repair?
an enzyme corrects a nucleotide alteration caused by a mutagen
e.g. , MGMT enzyme in humans, ADA enzyme + DNA photolyase in e.coli
what is excision repair?
- damaged nucleotide is completely removed + gap is filled via DNA synthesis
what are the 2 types of excision repair?
- base excision repair - a single altered base is removed
- nucleotide excision repair - a longer piece of DNA containing altered bases is removed
describe the mode of action of UvrABC endonuclease (e.coli repairman)
Identification
- damaged nucleotide causes helix distortion
- UvrAB trimer attaches
- subunit UvrC attaches, UvrA detaches
Excision
- segment is excised by UvrB and UvrC
- UvrB bridges gap until DNA pol I and DNA ligase can repair the strand completely
how can e.coli tell the difference between a template strand and daughter strands?
- parent molecules are methylated
- daughter strands are not yet methylated
How does mismatch repair occur?
- MutS and MutH attatch to the DNA
- MutH then cuts the DNA
- strand is removed by DNA helicase II
- DNA pol I and ligase repairs strand
