Chapter 6: Molecular Mechanisms of DNA Repair Flashcards
Mammalian cells have specialized pathways to sense, respond to and repair _____________ such as ___________________.
specific damage formats
base damage, SSBs, DSBs, sugar damage, DNA-DNA and DNA-protein crosslinks
There are different repair pathways for repairing DNA damage depending on _____________.
stage of the cell cycle
Eukaryotic cell mechanisms to restore the structural integrity of DNA includes
1.
2.
3.
4.
5.
6.
- direct repair of defects
- nucleotide excision repair
- base excision repair
- mismatch repair
- homologous recombination
- non-homologous end-joining
Nucleotide excision repair (NER) fixes ___________ such as ___________ produced by UV irradiation.
bulky lesions
pyrimidine dimers
Base excision repair (BER) repairs __________ and __________.
damaged bases
SSBs
Mismatch repairs corrects ____________ and ________ as they occur during _________.
mismatched nucleotides
small loops
replication
Homologous recombination repairs ___________.
DSBs
Non-homologous end-joining repairs ___________.
DSBs
The types of lesions caused by ionizing radiation are _________, __________, _________, _________, __________, _________, and _________.
base damage
AP sites
SSBs
DSBs
dimers
bulky adducts
base mismatches
Oxidative stress is the imbalance between _____________ and a biological systems ability to _____________.
production of ROS
detoxify the ROS/repair the resulting damage
Disturbances in the normal redox state of tissues can cause toxic effects through the production of __________ and ________ that _________ of the cell.
peroxides
free radicals
damage all components
Some ROS can act as messengers through ____________.
redox signaling
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 __________.
disease
sickle cell, Parkinsons, heart failure, Alzheimer’s, bipolar, etc.
attacking and killing pathogens
immune system
Superoxide is produced in significant amounts ____________.
intracellularly
The major reactive oxygen species (ROS) are ________, _________, __________, ________, __________, and _________.
singlet oxygen
superoxide
hydrogen peroxide
hydroxyl radical
nitric oxide
HOCl/HOBr/HOI
_____________ is formed after absorption of energy.
Singlet oxygen
Superoxide comes from _____________ from electron transport; activated ____________; __________ and __________.
leakage of electrons
phagocytes
xanthine oxidase
flavoenzymes
Superoxide is ________ oxidizing, _________ reductive.
weakly
mostly
___________ has similar binding energy to pre-hydrated electron. They both cause __________ damage.
Superoxide
reductive
The enzyme defenses for superoxide is __________. The products are __________.
superoxide dismutase
H2O2 + O2
Hydrogen peroxide is _________ oxidizing.
weakly
___________ is produced from superoxide via SOD.
hydrogen peroxide
________ is the major target of ionizing radiation however more research is being conducted on contribution of __________ damage to cell death induced by radiation.
DNA
cytoplasm
Irradiation of the cytoplasm perturbs ___________ which might contribute to the activation of ___________ that could impact upon the damaging effects of radiation.
intracellular metabolic redox reactions
protective or damaging processes
The free radicals produced by ionizing radiation are _______, ________, _______, and _______.
ROS
RNS
RHS (reactive halogenated species)
prehydrated electron
Transient generation of ROS/RNS/RHS has been detected within ________ of exposing the cell to IR.
minutes
________ and ________ are the sources for ROS/RHS/RNS.
mitochondrion
cytoplasm
__________ act as signaling molecules, ________ plays a role in immune defense.
ROS/RNS
RHS
amount of ROS produced by IR at clinically relevant radiation doses is __________ then the background (endogenous) ROS level produced by _____________ of the cell.
1000 fold lower
oxidative metabolism
The lethal radiation dose for a human body is _________.
4 Gy
The unit _______ is use for radiation dose.
Gy
ROS are generated during __________. Most damage _______ but sometimes _________. Most errors are _________ but some can _________.
respiration
can be repaired
there will be mistakes
silent
cause serious disease
If an amine group on DNA is moved, then there ____________ which causes damage.
cannot be H-bond
DNA is monitored by a swarm of proteins which ___________.
monitor the integrity
If DNA was not repairable, _________ could not exist.
life
Defects in damage sensing machinery/DNA repair processes can be correlated with ___________ of disease.
increase incidence
When bacteria are exposed to deadly doses of UV radiation they can suddenly recover if ____________.
illuminated with visible blue light
The two nucleotide excision repair pathways are __________ and __________.
global genome repair (GG-NER)
transcription-coupled repair (TC-NER)
GG-NER is ________ so lesions can be removed from DNA that ________ or ________ for genes.
genome-wide
encodes
does not encode
TC-NER only removes lesions in the DNA strands of ____________.
actively transcribed genes
TC-NER removes _________ from the site of damage to allow for repair of proteins.
RNA polymerase
The steps of NER are:
1. ___________
2. _________ that bracket the lesion.
3. __________ of the region containing the adducts.
4. ____________ in the gap region.
5. ____________.
damage recognition
DNA incisions
removal
repair synthesis
DNA ligation
A human equivalent to ________ helps set the circadian clock.
photolyase
DNA photolyase repairs ___________ and _________.
cyclobutane pyrimidine dimers
6-4 photoproducts
MMR removes ______ and ________ mismatches that occur during replication.
base-base
small insertion
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.
identification of mismatch by sensors
MMR factors are recruited
identified, incorrect/altered
resynthesis, ligation
Defects in DNA mismatch repair increases the risk of developing _____________.
hereditary colon cancer
pyrimidine dimers are caused by __________ not __________.
UV radiation
ionizing radiation
Base excision repair, homologous recombination and nonhomologous end joining _________ radiation damage.
repair
Nucleotide excision repair, transcription coupled repair and mismatch repair _________ radiation damage.
do not
DNA damage _______ mutation rate, _________ cell death. Mutations in XARCC1 ________ cell death.
increase
does not affect
increase
Defects in BER may lead to ________ mutation rate and ________ result in cellular radiosensitivity. Exception is __________ which _______ radiation sensitivity.
increased
do not
XRCC1
increases
Mutation in NER genes ________ lead to ionizing radiation sensitivity.
does not
DNA DSBs can be repaired by __________ and __________.
homologous recombination repair (HRR)
nonhomologous end joining (NHEJ)
HRR uses ____________ in repair as a template.
undamaged DNA strand
NHEJ mediates __________.
end to end joining
___________ is an error-free process. _________ is error-prone.
Homologous recombination
NHEJ
HRR primarily occurs in ________ whereas NHEJ occurs in _________. However they are not mutually exclusive and have been found active in ________.
late S/G2 phase
G1 phase
late S/G2 phase
DSB has _________ of total damage but is __________ because _________ to repair.
smaller fraction
more important
difficult
