Mutation and Repair 2
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| Define carcinogen. | A compound that causes cancer
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| Define mutagen. | A compound that interacts with DNA and causes a mutation
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| Mutagens are initiators or promoters? | Promoters
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| What are the two steps of cancer? | initiation and promotion
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| What changes the DNA in cancer? | An initiator
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| What happens if a mutagen is present at high concentrations? | Cell death - cell function is compromised.
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| What happens if a mutagen is present at low concentrations? | May result in a change in function of a gene product.
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| What influences the expression of the DNA damage in cancer? | Promoters
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| Which gene is involved in Cockayne syndrome? | XPB
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| Which gene is involved in trichothiodystrophy disease? | XPD
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| Why is 2-aminopurine (2AP) used in the treatment of cancer? | It can be prefertially incorporated into the rapidly dividing cancer cells and as the damage accumulates the cells are killed
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| Why is 6-mercaptopurine (6MP) used in the treatment of cancer? | It inhibits the process of DNA replication.
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| Why is cyclophosphamide (CP) used in the treatment of cancer? | CP alkylates the cancer cell DNA. Since abnormal repair is part of the reason the cancer exists in the first place, the bulky adduts are not removed and the accumulating damage kills he cells.
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| Why is estrogen a promoter? | It does not cause the DNA damage, but it activates breast tissue, favoring proliferation.
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| When is the Short Patch Repair used in Base Excision Repair? | When the sugar-phosphate backbone is not damaged.
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| When is the Long Patch Repair used in Base Excision Repair? | When the sugar-phosphate backbone is damaged.
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| When Cytosine residues spontaneously deaminate to the keto form, what base is produced? | Uracil
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| What recruits the TFIIH protein complex to the site of a bulky adduct during NER? | XPA/RPA
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| What recognizes the bulky adduct? | XPA and RPA
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| What is the basis of the Ames Test? | Measures the reversion frequency of a genetic mutation.
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| What bacteria is used in the Ames Test? | Salmonella that was aunable to grow on minimal medium in the absence of added histidine.
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| What are the two basic steps of the Ames Test? | Expose cells to a mutagen and plate on minimal medium without histidine.
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| Name the enzymes involved in the nucleotide excision repair in humans. | XPA/RPA, TFIIH protein complex (contains XPB and XPD), XPF exinuclease, XPG excinuclease, helicase, polymerase complex (DNA pol delta nad epsilon, PCNA, Replication Factor C {RPC}, DNA ligase
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| Name the enzymes involved in the nucleotide excision repair in E. Coli. | uvrABC excinuclease, DNA pol I, and ligase
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| List several examples of environmental causes of DNA mutations. | UV light, X-ray, man-made or natural toxins
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| How do cells become resistant to cyclophosphamide and other alkylating agents? | By direct reversal - they induce the production of MGMT.
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| Benzopyrene causes mutations in which base? | Guanine
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| Acrolein modifies guanine, leading to a _____________________. | G-->T transversion
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| Acrolein is ___________________. | One of the carcinogens found in cigarette smoke.
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| 6-Mercaptopurine (6MP), 2-aminopurine (2AP), and cyclophosphamide (CP) are used in the treatment of ________________. | Cancer
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| In humans, how does the repair system know which base is wrong? | Unknown, however, it may have something to do with Okazaki fragments.
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| A pyrimidine substituted by a purine is an example of a(n) ____________. | Transversion mutation
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| A purine substituted by a pyrimidine is an example of a(n) ____________. | Transversion mutation
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| When reactive oxygen species produce a damaged base such as 8-oxo-G, what kind of mutation does it lead to? | Transversion mutation
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| A purine substituted by a purine is an example of a(n) ____________. | Transition mutation
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| A pyrimidine substituted by a pyrimidine is an example of a(n) ____________. | Transition mutation
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| Why is a chemical first incubated in a liver extract during an Ames Assay? | Some mutagens are not mutagenic until they have been metabolized to the active
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| What are some of the problems with the Ames Test? | Some mutagens are not mutagenic until they have been metabolized to the active compound.
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| What protects the DNA when the olignucleotide fragment is taken off during the repair of a bulky adduct? | RPA (human ssb homolog)
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| If damage occurs to the phosphodiester backbone , what process is used to repair the break? | Recombination repair or non-homologous end joining (NHEJ)
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| What two general mechanisms are involved in the repair of double-strand breaks? | Recombination repair and non-homologous end joining (NHEJ)
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| BRCA2 is involved in what kind of repair of double-strand breaks? | Recombination repair
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| What are the advantages of the Ames Test? | Rapid; reasonable first approximation
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| What fills in part of the DNA in NHEJ? | polymerases
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| What enzyme is used to absorb a photon of light and cleave the cyclobutane ring during repair of pyrimidine dimers in bacteria and some lower eukaryotes? | photoreactivating enzyme
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| What enzymes in a liver extract metabolize a chemical to the active form during an Ames Assay? | P450 enzymes
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| What enzyme is used to repair alkylation of the O6 position of Guanine? | O6-methylguanine-DNA methyl transferase (MGMT)
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| In bacteria, what two ways are pyrimidine dimes repaired? | Nucleotide Excision Repair and Driect Reversal
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| Transcription-coupled repair is associated with which repair process? | Nucleotide Excision Repair
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| The Ku protein is involved in what kind of DNA repair? | Non-homologous end joining (NHEJ) in repair of double-strand breaks
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| Blunt ends are joined in what type of DNA repair? | Non-homologous end joining (NHEJ)
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| What protein recognizes and aligns the broken strands of DNA in Non-homologous end joining repair of double-strand breaks? | Ku
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| How is MGMT reactivated? | It's not. It is a stochiometric rather than a catalytic reaction.
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| If salmonella exposed to a certain chemical grows rapidly during an Ames assay, what does that say about the chemical? | It is highly mutagenic
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| What causes double strand breaks in DNA? | Ionizing radiation and other forms of oxidative damage
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| Where is XPB and XPD found? | In the TFIIH protein complex
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| What trims the ends in NHEJ? | Exonuclease
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| The polymerase complex which synthesizes new DNA during NER consists of _________. | DNA pols delta and epsilon, PCNA, and Replication factor C (RFC)
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| How is O6-Me-G repaired in humans? | direct reversal
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| How is O4-Me-T repaired in humans? | direct reversal
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| What gene product increases the chance of developing breast cancer when mutated? | BRCA2
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| XPF nicks the pohspohdiester backbone on the _______ side of the bulky adduct. | 5'
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| XPG nicks the pohspohdiester backbone on the _______ side of the bulky adduct. | 3'
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