Mutation and Repaoir
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| Xeroderma pigmentosum is caused by the inability to repair _____________. This is normally done by which repair process? | thymine dimers; Nucleotide Excision Repair
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| The major pyrimidne which forms cyclobutane dimers is ___________. | Thymine
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| Xeroderma pigmentosum is associated with increased incidence of skin cancers. Explain what kind of mutation has taken place. | There is a mutation in the nucleotide excision repair enzymes. Individuals with this genetic defect are unable to repair thymine dimers.
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| In E. coli, how does the repair system know which base is wrong? | The parent strand is methylated on A residues in the GATC sequence. The repair takes place on the unmethylated strand.
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| How do glycosidases know which bases should be removed by DNA? | The base is flipped out of the core of the double helix and into the active site of the enzyme. If the enzyme recognizes the damage, the glycosidic bond is hydrolyzed.
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| What are the four general steps of Mismatch Repair, Base Excision Repair, and Nucleotide Excision Repair? | Surveillance; Excision; Synthesis; and Ligase
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| What induces the enzymes of BER? | sublethal exposure to ionizing radiation and oxidative agents such as H2O2 or HOCl.
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| Which process uses DNA pol beta to fill in fresh nucleotides? | Short Patch Repair
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| Cyclobutane dimers occur on __________ (purines or pyrimidines). | Pyrimidines
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| DNA pol (beta, delta or epsilon) combines with what to synthesize new DNA in Long Patch Repair? | PCNA and RF/C
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| What kind of DNA repair mechanisms are malfunctioning in xeroderma pigmentosum? | Nucleotide excision repair of UV damage
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| Which kind of DNA repair is often referred to as bulky adducts? | Nucleotide Excision Repair
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| Which kind of DNA repair is the primary way of fixing mistakes that occur during transcription? | Nucleotide Excision Repair
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| What repair process repairs the formation of the benzopyrene adduct by cigarette smoke? | Nucleotide Excision Repair
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| What repair process repairs UV damaged DNA? | Nucleotide Excision Repair
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| Which repair process is often coupled to transcription? | Nucleotide Excision Repair
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| Cross-linking of bases to each other and to protein by oxidative damage and ionizing radiation are repaired by which process? | Nucleotide Excision Repair
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| Name the enzymes used in Long Patch BER. | N-glycosidases, AP endonucleases, DNA pol (beta, delta, or epsilon), PCNA, RF/C, Helicase, FEN1 endonuclease, DNA ligase
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| Name the enzymes used in Short Patch BER. | N-glycosidases, AP endonucleases, DNA pol (beta), DNA ligase
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| What enzymes are constantly moving along the DNA backbone scanning for the presence of damaged bases? | N-glycosidases and AP endonucleases
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| Which enzymes are common to both Short Patch and Long Patch BER? | N-glycosidase, AP endonuclease, DNA pol (beta), and DNA ligase
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| Most (90%) of HNPCC cases are due to genetic defects of either _________ or ________. | MSH2 or MLH1
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| What is the first step of the mismatch repair mechanism? | MSH complex recruits MLH and PMS proteins (requires ATP hydrolysis)
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| What step of mismatch repair requires ATP hydrolysis? | MSH complex recruits MLH and PMS proteins (requires ATP hydrolysis)
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| When one base is substituted for another, this is an example of ______________ mutation. | Missense
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| A transition mutation is an example of what kind of mutation? | Missense
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| A transversion mutation is an example of what kind of mutation? | Missense
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| What kind of DNA repair is used when the bases are mostly normal but they are just paired incorrectly? | Mismatch Repair
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| Which kind of DNA repair is the primary way of fixing mistakes that occur during replication? | Mismatch Repair
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| Which kind of DNA repair will fix short insertions/deletions? | Mismatch Repair
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| Which kind of DNA repair will fix O6-Me-G or O4-Me-T base modifications? | Mismatch Repair
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| Which process uses DNA pol (beta, delta or epsilon), PCNA and RF/C to replace bases excised by BER? | Long Patch Repair
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| When a reactive oxygen species oxidize C4 of the ribose and open the pyranose ring, what happens to the DNA? | It damages the sugar phosphate backbone
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| Frameshift mutations are typically caused by ______________ or _____________. | Insertions or deletions
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| Microsatellites are prone to what kind of mutations? | Insertions or deletions
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| Polymerase slippage results in what kind of mutation? | Insertions or deletions
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| A retrovirus inserting into the middle of a gene would be an example of a(n) ____________ mutation. | Insertion
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| "Base flipping" is associated with which enzyme. | Glycosidases
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| What does DNA pol beta do during Short Patch Repair? | fills in a fresh nucleotide and removes the AP nucleotide
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| What endonuclease clips the old piece out before DNA ligase can seal the nick in Long Patch Repair? | FEN1 endonuclease
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| What kind of DNA repair mechanisms are malfunctioning in hereditary nonpolyposis colon cancer (NHPCC)? | Enzymes that carry out mismatch repair.
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| What are the majority of our DNA insults due to? | Environmental damage.
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| The predominant mutation in cystic fibrosis is what kind of mutation? | Deletion
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| Why is thymine, rather than uracil part of DNA? | Cytosine can spontaneously deaminate to the keto form. This is uracil. If uracil was normally part of DNA, it would be hard to tell which residues were supposed to be uracil and which were supposed to be cytosine. The DNA would become scrambled.
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| How can U become a part of DNA? | Cytosine can spontaneously deaminate to the keto form. This is uracil.
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| What kind of adduct forms on the N10 position of guanine as a result of cigarette smoke? | Benzopyrene adduct
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| Which kind of DNA repair involves minor modifications to the bases? | Base Excision Repair
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| What process repairs small defects in single bases that may or may not cause small distortions? | Base Excision Repair
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| What process is important for removing uracil bases from DNA? | Base Excision Repair
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| The spontaneous deamination of cytosine to uracil is fixed by what process? | Base Excision Repair
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| What process is responsible for fixing the presence of N3-Me-A and N7-Me-G in DNA? | Base Excision Repair
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| What is the major repair mechanism for repairing oxidative damage to DNA? | Base Excision Repair
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| A nucleotide in DNA that does not have a base is called ____________. | Apurinic/apyrimidinc (AP) site
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| What is a transversion mutation. | A pyrimidine substituted by a purine, or a purine substituted by a pyrimidine
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| What is a transition mutation? | A purine substituted by a purine, or a pyrimidine substituted by a pyrimidine
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| What has to happen before a mutation to occur? | A change has t occur in both strands of the DNA
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| On which side of the AP site does the AP endonuclease clip the phosphodiester backbone? | 5' side
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| Outline the process of Base Excision Repair | 1. Distortion is recognized; 2. Altered base is removed; 3. AP endonuclease clips the backbone on the 5' side; 4. Site is repaired by Short Patch repair or Long Patch Repair
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| Outline the mismatch repair mechanism. | 1. MSH complex recruits MLH and PMS proteins, requires ATP hydrolysis; 2. Endonuclease nicks strand; 3. Helicase unwinds the DNA; 4. Exonuclease digests the nicked strand; 5. DNA pol fills the gap; 6. Ligase seals the nick
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| What five types of DNA repair mechanisms are we covering? | 1. Mismatch Repair; 2. Base Excision Repair; 3. Nucleotide Excision Repair; 4. Direct Reversal; 5. Repair of Double Strand Breaks
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| Which three of the DNA repair mechanisms we are studying work by similar mechanisms? | 1. Mismatch Repair; 2. Base Excision Repair; 3. Nucleotide Excision Repair
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| What two groups can cancers be classified as? | 1. loss of DNA repair functions; 2. chromosome instability
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| What two ways does DNA polymerase insure fidelity during replication? | 1. Base pairing rules; 2. Proofreading activity
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