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zzz - BIO107 - Cell and Molecular Biology > Finals - DNA Repair Mechanisms > Flashcards

Finals - DNA Repair Mechanisms Flashcards

1
Q

Different DNA repair mechanisms

A
  1. direct repair
  2. excision repair
  3. mismatch repair
  4. double-stranded break repair
  5. SOS response
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2
Q
  • involves chemical reversal of the damage without breaking the phosphodiester backbone of the DNA
  • not dependent on a template since the damage does not alter the sequence within which it occurs.
A

Direct repair

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3
Q

where direct repair happens

A
  1. nicks
  2. alkylation damage
  3. cyclobutyl dimers
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4
Q

sinlge-strand breaks in DNA where a phosphodiester bond is missing

A

nicks

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5
Q

repairs nicks

A

DNA ligase

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6
Q

what does DNA ligase do

A

glues phosphodiester bonds

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7
Q
  • repaired through enzymatic transfer of alkyl group from nucleotide to their own polypeptide chains
  • removed by ADA
A

alkylation damage

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8
Q

ADA

A

Adenosine deaminase

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9
Q

Ex of alkylation damage repair

A
  1. ADA enzyme of E. coli
  2. Human MGMT
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10
Q

MGMT

A

methyl guanine – DNA methyl transferase

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11
Q

what does ADA do

A
  • removes methyl and puts it on its cystein residue
  • alkylated base is free from alkyl
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12
Q

what does human MGMT do

A

interacts with alkylating agents during chemotherapy

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13
Q
  • repaired by DNA photolyase
  • need presence of light
A

cyclobutyl dimers

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14
Q

what repairs cyclobutyl dimers

A

DNA photolyase

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15
Q
  • perhaps the best known DNA lesion affecting a single DNA strand
  • it is an intrastrand cross-link in which two adjaent pyrimidines are connected by a cyclobutane ring
A

pyrimidine dimer (PD)

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16
Q

where pyrimidine dimer most frequently form

A

two thymines (thymine dimer)

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17
Q

Steps in direct repair of cyclobutyl dimers

A
  1. Photolyase needs to be activated by UV. Chromophore abosorbs UV light and energy is transfered to FADH (noncovalent bonding).
  2. FADH’s electron is transferred to pyrimidine dimer causing it to split
  3. Restores and hydrogen bonds are formed (renaturation)
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18
Q

UV wavelength in activation of photolyase

A

320-370nm

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19
Q

wavelength chromophore absorbs

A

300-500nm

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20
Q

involves excision of a single damaged base, followed by resynthesis

A

base excision repair

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21
Q

Enzymes in base excision repair

A
  1. DNA glycosylase
  2. AP endonuclease
  3. DNA polymerase β
  4. DNA ligase
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22
Q
  • involved in the removal of damaged base
  • creates AP site
A

DNA glycosylase

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23
Q

what does DNA glycosylase create

A

apurinic/apyrimidinic site (AP site)

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24
Q

incise posphodiester backbone adjacent to AP site

A

AP endonuclease

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25
Q
  • fill the gap created during base excision repair
  • incorporate nucleotide
A

DNA polymerase β

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26
Q

seals the backbone during base excision repair

A

DNA ligase

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27
Q

Summary of Base Excision Repair

A
  1. DNA glycosylase removes damaged base and creates apurinic/apyrimidinic site (AP site)
  2. AP endonuclease incise phophodiester backbone adjacent to AP site
  3. DNA pol β fill the gap by incorporating nucleotide
  4. DNA ligase seals nick
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28
Q
  • repairs damage affecting longer strands, 2-30 bases
  • used by the ell for bulky DNA damage
A

Nucleotide excision repair

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29
Q

length of damage during nucleotide excision repair

A

2-30 bases

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30
Q

nucleotide excision repair is used by the cell for what?

A

bulky DNA damage

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31
Q

mediated by gene products of uvrA, uvrB, or uvrC

A

NER in bacteria

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32
Q
  • involves XPA, XPB, XPC, XP6 proteins
  • CSA and CSB proteins
  • ERCC7, RPA, and RAD 23 proteins
A

NER in eukaryotes

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33
Q

inherited condition characterized by an extreme sensitivity to ultraviolet radiation (UVR), which is present in sunlight and may also be found in some types of artificial lighting

A

Xeroderma pigmentosum

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34
Q

what is absent in people with Xeroderma pigmentosum

A

Nucleotide excision repair (NER)

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35
Q

Summary of Nucleotide Excision Repair

A
  1. uvrB with uvrA scans damaged DNA
  2. uvrA helps uvrB recognize damaged part
  3. uvrA released, uvrC attaches, helicase II unwinds
  4. uvrC with uvrB excise the damaged part and some nucleotides near are also cut
  5. uvrB bridges the gap
  6. DNA pol I incorporate complemetary nucleotides
  7. DNA ligase seal nicks
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36
Q

Nucleotide excision repair (NER):
scans damaged DNA

A

uvrB with uvrA

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37
Q

Nucleotide excision repair (NER):
helps uvrB recognize damaged part

38
Q

Nucleotide excision repair (NER):
what happens after recognition of damaged part

A
  • uvrA released, uvrC attaches
  • helicase II unwinds
39
Q

Nucleotide excision repair (NER):
- excise or cut the damaged part
- some nucleotides near the damaged are also excised

A

uvrC with uvrB

40
Q

Nucleotide excision repair (NER):
bridges the gap

41
Q

Nucleotide excision repair (NER):
incorporate complementary nucleotides

42
Q

Nucleotide excision repair (NER):
ligate nicks

A

DNA ligase

43
Q
  • happens in new strand DNA
  • corrects mismatched nucleotide
  • strand specific
  • repairs new strand DNA -? methylation pattern
A

Mismatch Repair

44
Q

serves as guide to find damage during mismatch repair

A

methylation pattern

45
Q

Essential MMR proteins in prokaryotes

A
  1. Mut S
  2. Mut H
  3. Mut L
46
Q

MisMatch repair prokaryotes:
recognizes mismatched bp

47
Q
  • MisMatch repair prokaryotes:
    very weak endonuclease, activated when bound to Mut L
  • distinguish the strand containing mismatch
48
Q

forms complex with Mut S and Mut H

49
Q

Essential MMR proteins in eukaryotes

A
  1. Msh 2/ Msh 6
  2. Msh 2 / Msh 3
50
Q

MisMatch repair:
detects mismatch

51
Q

MisMatch repair prokaryotes:
serve as a guide for Mut H

A

methyl group (already programmed)

52
Q

MisMatch repair prokaryotes:
needed for mut L to work

A

MutH and MutS

53
Q

MisMatch repair prokaryotes:
site where there is a methyl group (complementary)

54
Q

MisMatch repair prokaryotes:
unwinds

A

DNA helicase II

55
Q

MisMatch repair prokaryotes:
cuts

A

exonuclease (Mut H)

56
Q

MisMatch repair in humans

A
  1. short mismatch
  2. long mismatch
57
Q

short mismatch

A

MSH2 & MSH6

58
Q

long manuscript

A

MSH2 & MSH3

59
Q

Mismatch repair in humans steps

A
  1. mismatch
  2. recognition
  3. sliding clamp
  4. exonuclease
  5. resynthesis
60
Q
  • creates complex to lock mismatch
  • ATP is used
A

MSH2 & MSH6

61
Q

Mismatch Repair:
pushes DNA pol

A

sliding clamp

62
Q

Mismatch Repair:
- cuts from mismatch towards 3’
- removes mismatch DNA

A

exonuclease I

63
Q

Mismatch Repair:
fills in gap

A

DNA pol delta

64
Q

recombination is a form of ds break repair

A

double-stranded break repair

65
Q

Two types of double-stranded break repair

A
  1. homologous recombination
  2. non-homologous end-joining
66
Q

Homologous recombination:
break are equal

A

blunt-end break

67
Q

Homologous recombination:
- cut the blunt-end further
- creates overhangs or sticky ends that are easier to complement

A

5’-3’ exonuclease

68
Q

Homologous recombination:
forms displacement loop

A

strand invasion

69
Q

Homologous recombination:
promotes formation of displacement loop

70
Q

Homologous recombination steps

A
  1. ds-break
  2. 5’-3’ exonuclease
  3. strand invasion
  4. DNA synthesis
  5. ligation
  6. branch migration
71
Q
  • growing list of enzymes are involved
  • time requiring
  • some nucleotide will be lost, degraded
  • introduce deletions
A

non-homologous end-joining in humans

72
Q

enzyme in non-homologous end joining

A

DNA end-processing enzymes

73
Q

Non-homologous end-joining:
binds to the break

74
Q

Non-homologous end-joining:
activates XRCC4 protein

75
Q

Non-homologous end-joining:
- DNA-end processing enzyme
- trim/fill the gaps to make the ends compatible for ligation

76
Q

Non-homologous end-joining:
needed to activate ligase

A

XRCC4-Ligase IV complex

77
Q

Non-homologous end-joining:
- interact to XRCC4-ligase IV complex
- stimulate ligase activity of LIgase IV

A

cernunnos-XLF

78
Q

Non-homologous end-joining:
aligned and ligated

79
Q
  • in bacteria
  • inducible
  • allows DNA replication to proceed through a highly damaged region
  • by-passes DNA damage* error-prone
A

SOS response

80
Q

initiation of the SOS response

A
  1. activation of RecA
  2. degradation and inactivation of LexA
  3. expression of DNA polymerase V
81
Q
  • acts as protease when bound to ds DNA
  • binds ssDNA
A

activation of RecA

82
Q
  • lexA is the repressor of RecA gene when RecA protein is not needed.
  • when there is extensive damage, RecA is producd
A

Degradation and inactivation of LexA

83
Q

umuD and umuC proteins

A

expression of DNA pol V

84
Q

complex of proteins that answers mutation problems

85
Q

SOS response:
produced when there is extensive damage

86
Q

how is SOS response inactivated with Lex A

A

LexA represses all genes that are involved in SOS response.

87
Q

SOS response:
degrades lexA to activate the genes. This will be translated into SOS proteins

A

initiation of the SOS response

88
Q

SOS response:
- main SOS protein
- no sense of proof-reading

89
Q

gene for DNA pol V

90
Q

what happens when there are mutations

A
  1. accumulate mutation
  2. no efficient repair
  3. advantage/deleterious

zzz - BIO107 - Cell and Molecular Biology (21 decks)

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