6 DNA damage, repair, and mutations Flashcards

(56 cards)

1
Q

what are somatic mutation

A

mutations in body that only impact you

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2
Q

What are germinal mutations

A

get transmitted to further generation

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3
Q

what are 2 ways tp get a mutant DNA sequence

A

DNA damage –> turns into mutant DNA
DNA Repair messes up and created a mutant DNA

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4
Q

what is the origin and frequency of mutation

A

○ Mostly from replication errors
○ Polymerase makes mistakes

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5
Q

what are some causes of spontaneous mutation rate

A

○ Genome characteristics
○ Cell age

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6
Q

what are induced mutations

A

○ Happens in higher frequency
○ From known chemical and physical reagents
○ Base analogs
§ Imposter nucleuotides
○ Hydroxylating, alkylation, deaminating agents
○ UV and ionizing radiation

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7
Q

what are 3 types of mutations

A

○ SBP (single base pair)
○ SNP (single nucleotide polymorphism)
○ Point mutations (SNP and SBP)

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8
Q

what are 3 types of point mutations

A
  • Transition mutations
  • Transversion mutations
  • Indels
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9
Q

what is a transition Point mutation

A

□ Purine –> purine (A=G, G=A)
□ Pyr –> pyr (A=T, T=A)

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10
Q

what is a transversion point mutation

A

□ Purine <–> pyrimidine

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11
Q

what is an indel point mutation

A

Deletion or insertion of a base

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12
Q

what are synonymous mutations

A

○ Silent mutations = nothing happens

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13
Q

what are non-synonymous mutations (sense)

A

○ Missense mutations = code for a diff AA
○ Nonsense mutations = changes to a stop codon (likely severe)

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14
Q

what is a frameshift mutation

A
  • Frameshift = removal, addition, or substitution
    ○ Disrupts triplet reading frame
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15
Q

what does a non-coding region mutation do

A

Affects gene expression

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16
Q

what is slippage

A

Polymerase accidentally moves on the dna up or down causing insertion or deletion on strand its synthesizing

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17
Q

what are 6 types of nucleotide mispairing

A
  • tautomers
  • ionization
  • wobble bases
  • depurination
  • deamination
  • oxidative damage
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18
Q

what is a tautomer

A

Isomeric changes in chemical shape

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19
Q

what is ionization in nucleotide mispairing

A

Gain or loss of electrons changes binding pattern (ex. T binds to G)

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20
Q

what are wobble bases in nucleotide mispairing

A

Can sometimes fuck up

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21
Q

what is depurination of nucleotide mispairing

A

Removal of a purine
Stops replication and transcription

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22
Q

what is deamination

A

Removal of amine (NH2) grp
Alters base pairing

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23
Q

what is oxidative damage

A

□ Directly breaks DNA dbl strand

24
Q

what are induced mutation (what is the inducer)

A

○ Mutagen: chemical or physical force that increases chance of mutation
§ Replace alter or damage base in dna

25
what are sometypes of chemical and physical mutations
Chemical - alkylating agents - reactive oxygen species - intercalating agents - Base analogs Physical - UV/Ionizing radiation
26
what happens when UV light hits a DNA strand
○ Covalently links neighbouring pyrimidines ○ Stops replication ○ Results in transition mutations
27
what happens when ionizing radiation hit DNA
○ "lightning bolts hitting DNA" - Likely to cause actual breaks in DNA
28
what is an alkylating agent in chemical mutagens
addition of alkyl grp to a nucleotide - disrupts correct base pairing
29
what is a base analog in chemical mutagens
Chemically similar to ATCG(imposter) - can be incorrectly incorporated into DNA polymerase
30
what is a intercalating agent (mutagen)
Inserts between base pairs - distorts dbl helix - increases slippage
31
what is an Abasic site
○ Nucleotide been removed and theres jus a hole in the DNA
32
what is the non bulky DNA damage and the bulky DNA damage
NON-BULKY - alkylation - oxidation - deamination - depurination BULKY - pyrimidine dimer - bulky adduct - base mismatch - loop - dbl strand break
33
what is a revertant
WT that have been mutants and are now WT again
34
what is the mutagenicity ratio (MR)
total # revertants / # spontaneous revertants
35
if a compound has no mutagenic effect the MR is
~ 1
36
if a compound shows signs of being mutagenic the MR is
MR > 1
37
if a compound kills the cell the MR is
MR < 1
38
How can we fix the non-bulky damage in DNA
Base excision repair
39
how can we fix a pyrimidine dimmer and a bulk adduct
Nucleotide excision repair - (pyrimidine dimmer can also be fixed by direct repair)
40
what does the mechanism of mismatch repair fix ?
base mismatch and loop
41
what does non-homologous end joining repair ?
double stranded break
42
what are the steps taken when DNA has been damaged
- surveillance(detect errors) - Excision (Find mistake and cut it out) - polymerization (replace what was cut) - strand ligation (reconnect bonds in repaired stand)
43
what is direct repair
○ Some errors can be reverted by using specific enzymes because they happen so often
44
what is base excision repair
○ One of the simplest way to repair ○ Detection and excision § Enzyme removes the whole error § Cut strand with endonuclease to allow DNA entry to fix § Polymerase replaces error with correct base § Can replace 1 base or a whole chunk
45
what is nucleotide excision repair
For larger damage that affects multiple base pairs § Damage detection □ Global genome surveillance finds □ Look for stalled RNA polymerase § Strand separation □ Helicase opens DNA § excision □ Endonuclease cuts out whole chunk § Polymerization □ Polymerase fixes § Ligation □ Glued back together by DNA ligase
46
what is mismatch repair (what does it look for)
○ Uses concept of DNA methylation ○ Detection § Template strand has a methyl group and new strand doesn’t so we know which one is right
47
what are double stranded breaks
○ Most serious of damage ○ Affects both strands so theres no template
48
what are 2 ways to fix a double stranded break
homologous recombination (HR), non homologous End Joining (NHEJ)
49
what are traits of homologous recombination (HR)
§ Uses homo chromos as template § Active post DNA replication § More error proof
50
what are traits of non homologous End Joining (NHEJ)
§ DNA strands join independent of complementarity § Active in dividing and non dividing cells § Doesn’t req template strand § More prone to errors § DNA strands jus glued together
51
how does NHEJ work
○ Detection § Proteins bind to end to supress further damage ○ Strand resection § Recruit of kinase and nuclease proteins to make blunt ends ○ Polymerization § Polymerase fills end for ligation (sticky ends) § Does not add bases (no template) ○ Ligation § Ligates the 2 sticky ends together
52
how does HR repair work
○ Detection § Same way NHEJ ○ Strand resection § Cuts back from break § Creates 3' overhangs (sticky ends) ○ Strand exchange/invastion § Seperates double stranded DNA § Forms a Displacement loop (D-Loop) ○ Polymerization § Missing DNA copied from template ○ 2 complex pathways from here § Synthesis dependant strand annealing pathway (SDSA) § Double strand break repair pathway (DSBR)
53
what is Synthesis dependant strand annealing pathway (SDSA)
- both strands broken - One broken strand "invades" a matching DNA strand to use as template. - The broken strand copies the missing DNA using the intact strand as guide. - The newly made DNA strand separates and sticks back to its original partner strand. - No Crossing-Over: Unlike other repair methods, SDSA does not swap large sections of DNA between chromosomes, avoiding genetic changes.
54
what is Double strand break repair pathway (DSBR)
It’s like repairing a torn rope by using a similar rope to guide the fix, but sometimes parts of the ropes get exchanged.
55
what is the only repair mechanism that doesnt use a polymerase
Direct repair - uses enzymes
56
TF NHEJ doesnt use a template strand and HR does
T