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38 Cards in this Set
- Front
- Back
irreversible state of dormancy for a cell
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senescence
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three outcomes of too much DNA damage
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apoptosis, senescence, unregulated cell division forming a tumor (cancer)
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unfiltered sunlight causes this damage to dna
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pyrimidine dimers
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procarcinogen that intercalates into DNA, covalently bonding to the guanine bases at the N2 position, distorting the DNA
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benzo[a]pyrene
active form is benzo[a]pyrene diol epoxide |
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base deamination is a type of DNA damage that turns each of these into
Cytidine Adenine Guanine 5-methyl cytosine |
Cytidine to uracil
Adenine to hypoxanthine Guanine to xanthine 5-methyl cytosine to thymine |
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chemical modification of bases by ROS reactive oxygen species: can turn thymine into
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thymine glycol
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normal metabolism leads to this dna modification
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alkylation
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normal biological methyl group donor thatreacts accidentally with DNA to produce alkylated bases like 3-methyladenine
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S-adenosylmethionine
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three steps of dna repair
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recognize specific forms of DNA damage, remove damage, and repair it
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patients with xeroderma pigmentosum lack this form of repair
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nucleotide excision repair
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werner syndrome, which produces early aging, has a problem with this part of DNA repair
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helicase
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single bases in DNA can be chemically changed, for example by deamination or alkylation, resulting in incorrect base-pairing. base excision repair involves first flipping the mutated base out of the DNA helix and then repairing the base alone.
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base excision repair
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this system recognizes bulky modifications of bases, such as uv thymine dimers, which distort the shape of the DNA helix. this system removes a short single stranded dna segment that includes the lesion, creating a single strand gap in the DNA, which is filled by DNA polymerase
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Nucleotide excision repair
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these enzymes regconize and repair erroneous insertion, deletion and misincorporation of bases that can arise during DNA replication and recombination.
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mismatch repair
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three enzymes essential for Base Excision Repair (BER)
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DNA glycosylase
AP endonuclease deoxyribose-phosphate lyase |
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this enzyme in BER removes damanged DNA bases by cleaving the N glycosidic bond between the target base and deoxyribose to create an AP site (apurinic/apyriminic)
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DNA glycosylase
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BER enzyme that recognizes the AP site and nicks the damaged DNA on the 5' side (upstream) of the AP site
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AP endonuclease
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BER enzyme that removes the single, empty, sugar-phosphate residue. then dna polymerase and dna ligase complete the repair process
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deoxyribose - phosphate lyase
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what enzyme in BER has many forms to cut out many different errors?
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DNA glycoslyase
each recognize different damaged bases, like oxoG (oxidated guanosine) (there are two, one that removes from C and one that removes from A) also one for uracil, one for thymine to guanine, and others |
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how to fix pyrimidine dimers
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nucleotide excision repair
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six steps of NER
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1. damage recognition
2. binding of a multi-protein complex at the damaged site 3. double incision of the damaged strand several nucleotides away from the damaged site, on both the 5' and 3' sides 4. removal of the damage-containing oligonucleotide from between the two nicks 5. filling in of the resulting gap by DNA polymerase 6. ligation |
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three diseases associated with NER defects
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Xeroderma pigmentosum
cockayne's syndrome trichothiodystrophy |
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NER of pyrimidine dimer in e coli:
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1. uv specific endonuclease uvrABC ase recognizes the dimer, and cleaves the damaged strand at the phosphodiester bonds on both the 5'side and the 3' side of the dimer
2. damaged nucleotide is released, leaving a gap in DNA 3. gap filled by DNA pol I 4. nick sealed by ligase |
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in DNA mismatch repair, how do we know which is right base and which is wrong?
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strands are hemimethylated; parent strand is methylated, daughter strand is not methylated yet, so we can easily tell
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dna mismatch repair fixes what issues?
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erroneous insertion, deletion, and mis incorporation of bases as well as some forms of DNA damage
mismatched bases are G/T, A/C, and base insertion/deletion loops (IDLs) |
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in MMR, what base is methylated, and what bases are considered mismatches when methylated?
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adenine is methylated
methylated C and G are considered mismatches |
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what do these proteins do
MutS, MutL, Mut... |
all Mut deal with mismatch repair
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MMR protein for damage recognition
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MutS
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MMR protein that is endonuclease
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MutH
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MMR protein DNA helicase
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MutU
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what polymerase is used in MMR
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DNA Pol III
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in MMR, couples the replicative machinery
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PCNA
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lynch syndrome AKA HNPCC is
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hereditary nonpolyposis colorectal cancer
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HNPCC is known to be associated with mutations in genes involved in the ...
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DNA mismatch repair pathway
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how does cysplatin work
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binds to the dna strand, forming a bubble that could be cut out by MMR, so it is better if cancer does not have MMR
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this system uses the enzymes that normally perform genetic recombination between homologous chromosomes during meiosis
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homologous recombination repair
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pathway that repairs double strand breaks in DNA, most common for double strand breaks
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NHEJ - nonhomologous end-joining repair of
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which dna repair mechanism is the only one that is error prone
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NHEJ
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