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PHYS 395 > Chapter 6: Molecular Mechanisms of DNA Repair > Flashcards

Chapter 6: Molecular Mechanisms of DNA Repair Flashcards

1
Q

Mammalian cells have specialized pathways to sense, respond to and repair _____________ such as ___________________.

A

specific damage formats
base damage, SSBs, DSBs, sugar damage, DNA-DNA and DNA-protein crosslinks

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2
Q

There are different repair pathways for repairing DNA damage depending on _____________.

A

stage of the cell cycle

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3
Q

Eukaryotic cell mechanisms to restore the structural integrity of DNA includes
1.
2.
3.
4.
5.
6.

A
  1. direct repair of defects
  2. nucleotide excision repair
  3. base excision repair
  4. mismatch repair
  5. homologous recombination
  6. non-homologous end-joining
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4
Q

Nucleotide excision repair (NER) fixes ___________ such as ___________ produced by UV irradiation.

A

bulky lesions
pyrimidine dimers

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5
Q

Base excision repair (BER) repairs __________ and __________.

A

damaged bases
SSBs

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6
Q

Mismatch repairs corrects ____________ and ________ as they occur during _________.

A

mismatched nucleotides
small loops
replication

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7
Q

Homologous recombination repairs ___________.

A

DSBs

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8
Q

Non-homologous end-joining repairs ___________.

A

DSBs

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9
Q

The types of lesions caused by ionizing radiation are _________, __________, _________, _________, __________, _________, and _________.

A

base damage
AP sites
SSBs
DSBs
dimers
bulky adducts
base mismatches

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10
Q

Oxidative stress is the imbalance between _____________ and a biological systems ability to _____________.

A

production of ROS
detoxify the ROS/repair the resulting damage

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11
Q

Disturbances in the normal redox state of tissues can cause toxic effects through the production of __________ and ________ that _________ of the cell.

A

peroxides
free radicals
damage all components

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12
Q

Some ROS can act as messengers through ____________.

A

redox signaling

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13
Q

Oxidative stress in humans can be negative as it is involved in ___________ such as _____________. However it can also be positive in that they are used for __________ by __________.

A

disease
sickle cell, Parkinsons, heart failure, Alzheimer’s, bipolar, etc.
attacking and killing pathogens
immune system

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14
Q

Superoxide is produced in significant amounts ____________.

A

intracellularly

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15
Q

The major reactive oxygen species (ROS) are ________, _________, __________, ________, __________, and _________.

A

singlet oxygen
superoxide
hydrogen peroxide
hydroxyl radical
nitric oxide
HOCl/HOBr/HOI

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16
Q

_____________ is formed after absorption of energy.

A

Singlet oxygen

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17
Q

Superoxide comes from _____________ from electron transport; activated ____________; __________ and __________.

A

leakage of electrons
phagocytes
xanthine oxidase
flavoenzymes

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18
Q

Superoxide is ________ oxidizing, _________ reductive.

A

weakly
mostly

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19
Q

___________ has similar binding energy to pre-hydrated electron. They both cause __________ damage.

A

Superoxide
reductive

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20
Q

The enzyme defenses for superoxide is __________. The products are __________.

A

superoxide dismutase
H2O2 + O2

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21
Q

Hydrogen peroxide is _________ oxidizing.

A

weakly

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22
Q

___________ is produced from superoxide via SOD.

A

hydrogen peroxide

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23
Q

________ is the major target of ionizing radiation however more research is being conducted on contribution of __________ damage to cell death induced by radiation.

A

DNA
cytoplasm

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24
Q

Irradiation of the cytoplasm perturbs ___________ which might contribute to the activation of ___________ that could impact upon the damaging effects of radiation.

A

intracellular metabolic redox reactions
protective or damaging processes

25
Q

The free radicals produced by ionizing radiation are _______, ________, _______, and _______.

A

ROS
RNS
RHS (reactive halogenated species)
prehydrated electron

26
Q

Transient generation of ROS/RNS/RHS has been detected within ________ of exposing the cell to IR.

A

minutes

27
Q

________ and ________ are the sources for ROS/RHS/RNS.

A

mitochondrion
cytoplasm

28
Q

__________ act as signaling molecules, ________ plays a role in immune defense.

A

ROS/RNS
RHS

29
Q

amount of ROS produced by IR at clinically relevant radiation doses is __________ then the background (endogenous) ROS level produced by _____________ of the cell.

A

1000 fold lower
oxidative metabolism

30
Q

The lethal radiation dose for a human body is _________.

A

4 Gy

31
Q

The unit _______ is use for radiation dose.

A

Gy

32
Q

ROS are generated during __________. Most damage _______ but sometimes _________. Most errors are _________ but some can _________.

A

respiration
can be repaired
there will be mistakes
silent
cause serious disease

33
Q

If an amine group on DNA is moved, then there ____________ which causes damage.

A

cannot be H-bond

34
Q

DNA is monitored by a swarm of proteins which ___________.

A

monitor the integrity

35
Q

If DNA was not repairable, _________ could not exist.

A

life

36
Q

Defects in damage sensing machinery/DNA repair processes can be correlated with ___________ of disease.

A

increase incidence

37
Q

When bacteria are exposed to deadly doses of UV radiation they can suddenly recover if ____________.

A

illuminated with visible blue light

38
Q

The two nucleotide excision repair pathways are __________ and __________.

A

global genome repair (GG-NER)
transcription-coupled repair (TC-NER)

39
Q

GG-NER is ________ so lesions can be removed from DNA that ________ or ________ for genes.

A

genome-wide
encodes
does not encode

40
Q

TC-NER only removes lesions in the DNA strands of ____________.

A

actively transcribed genes

41
Q

TC-NER removes _________ from the site of damage to allow for repair of proteins.

A

RNA polymerase

42
Q

The steps of NER are:
1. ___________
2. _________ that bracket the lesion.
3. __________ of the region containing the adducts.
4. ____________ in the gap region.
5. ____________.

A

damage recognition
DNA incisions
removal
repair synthesis
DNA ligation

43
Q

A human equivalent to ________ helps set the circadian clock.

A

photolyase

44
Q

DNA photolyase repairs ___________ and _________.

A

cyclobutane pyrimidine dimers
6-4 photoproducts

45
Q

MMR removes ______ and ________ mismatches that occur during replication.

A

base-base
small insertion

46
Q

The process of MMR is:
1. ____________ that transduce the signal of a mismatched base pair.
2. ____________.
3. Newly synthesized strand harboring mismatch is __________ and _________ nucleotides are excised.
4. ________ and _______ of excised DNA tract is completed.

A

identification of mismatch by sensors
MMR factors are recruited
identified, incorrect/altered
resynthesis, ligation

47
Q

Defects in DNA mismatch repair increases the risk of developing _____________.

A

hereditary colon cancer

48
Q

pyrimidine dimers are caused by __________ not __________.

A

UV radiation
ionizing radiation

49
Q

Base excision repair, homologous recombination and nonhomologous end joining _________ radiation damage.

A

repair

50
Q

Nucleotide excision repair, transcription coupled repair and mismatch repair _________ radiation damage.

A

do not

51
Q

DNA damage _______ mutation rate, _________ cell death. Mutations in XARCC1 ________ cell death.

A

increase
does not affect
increase

52
Q

Defects in BER may lead to ________ mutation rate and ________ result in cellular radiosensitivity. Exception is __________ which _______ radiation sensitivity.

A

increased
do not
XRCC1
increases

53
Q

Mutation in NER genes ________ lead to ionizing radiation sensitivity.

A

does not

54
Q

DNA DSBs can be repaired by __________ and __________.

A

homologous recombination repair (HRR)
nonhomologous end joining (NHEJ)

55
Q

HRR uses ____________ in repair as a template.

A

undamaged DNA strand

56
Q

NHEJ mediates __________.

A

end to end joining

57
Q

___________ is an error-free process. _________ is error-prone.

A

Homologous recombination
NHEJ

58
Q

HRR primarily occurs in ________ whereas NHEJ occurs in _________. However they are not mutually exclusive and have been found active in ________.

A

late S/G2 phase
G1 phase
late S/G2 phase

59
Q

DSB has _________ of total damage but is __________ because _________ to repair.

A

smaller fraction
more important
difficult

PHYS 395 (13 decks)

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