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Mutations & DNA Repair Systems

Tier 3 · #20 of 33 · moderate yield · topic 2.4 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    What is the single most common cause of spontaneous DNA replication errors ?
    Back
    Tautomerism
  2. Front
    In tautomerism , which rare tautomeric form of a base tricks DNA polymerase into misincorporation?
    Back
    The enol/imino form
  3. Front
    Enol-thymine is misread by DNA polymerase as which base?
    Back
    Cytosine
  4. Front
    Spontaneous deamination of cytosine produces which base?
    Back
    Uracil
  5. Front
    How many cytosines undergo deamination per cell per day?
    Back
    Roughly 70–200
  6. Front
    If deaminated cytosine (now uracil ) is unrepaired, the next polymerase reads it as thymine — fixing which permanent mutation?
    Back
    A C→T transition
  7. Front
    Deamination of adenine produces which altered base?
    Back
    Hypoxanthine
  8. Front
    Which chemical agent externally induces deamination by attacking amino groups directly?
    Back
    Nitrous acid (HNO₂)
  9. Front
    Depurination is the hydrolytic cleavage of which bond?
    Back
    The N-glycosidic bond ( purine base to deoxyribose )
  10. Front
    The loss of a purine base from the sugar leaves behind what kind of lesion?
    Back
    An AP (apurinic) site
  11. Front
    How many AP sites are created per cell per day by depurination ?
    Back
    Roughly 10,000
  12. Front
    Unrepaired AP sites can collapse into what kind of DNA break?
    Back
    Single-strand breaks (SSBs)
  13. Front
    UV radiation at which wavelength is absorbed by pyrimidines to cause DNA damage?
    Back
    260 nm
  14. Front
    What specific lesion does UV light form by fusing adjacent thymines on the same strand?
    Back
    Cyclobutane pyrimidine dimer (thymine dimer)
  15. Front
    Does a thymine dimer cause a point mutation on its own, or a replication block?
    Back
    A replication block (blocks DNA and RNA polymerase )
  16. Front
    Ionizing radiation (X-rays, gamma rays) damages DNA chiefly by generating what?
    Back
    Reactive oxygen species (especially hydroxyl radicals, •OH )
  17. Front
    What is the most clinically significant oxidative base lesion ?
    Back
    8-oxoguanine (8-oxoG)
  18. Front
    During replication, 8-oxoguanine mispairs with which base instead of cytosine ?
    Back
    Adenine
  19. Front
    8-oxoguanine mispairing with adenine produces which type of mutation?
    Back
    A GC→TA transversion
  20. Front
    Which mutation type does p53 most commonly carry in tumors , linked to 8-oxoguanine ?
    Back
    G→T transversion
  21. Front
    What is the most important alkylating-agent lesion for the exam?
    Back
    O6-methylguanine (O6-meG)
  22. Front
    O6-methylguanine base-pairs with which base instead of cytosine ?
    Back
    Thymine
  23. Front
    O6-methylguanine mispairing produces which mutation after one round of replication?
    Back
    A GC→AT transition
  24. Front
    Which chemotherapeutic alkylating agent is named as a source of O6-methylguanine ?
    Back
    Melphalan
  25. Front
    Polycyclic aromatic hydrocarbons (PAHs) are activated into reactive DNA-binding metabolites by which enzymes?
    Back
    Cytochrome P450 enzymes
  26. Front
    PAH bulky adducts form preferentially on which base?
    Back
    Guanine
  27. Front
    Which mycotoxin from mold on stored grain forms bulky guanine adducts and is linked to liver cancer ?
    Back
    Aflatoxin B1
  28. Front
    Aflatoxin B1 generates which signature mutation in tumor suppressors like p53 ?
    Back
    G→T transversions
  29. Front
    Cloze: A ______ swaps one purine for another or one pyrimidine for another (A↔G or C↔T).
    Back
    transition
  30. Front
    Cloze: A ______ swaps a purine for a pyrimidine or vice versa.
    Back
    transversion
  31. Front
    Are transitions or transversions more common, and why?
    Back
    Transitions — they require less geometric distortion at the base pair
  32. Front
    A codon change that yields the same amino acid (via code degeneracy) is which mutation type?
    Back
    Silent (synonymous)
  33. Front
    A substitution to an amino acid with different properties that usually impairs function is which type?
    Back
    Non-conservative missense
  34. Front
    A substitution that changes a codon to a STOP codon is which mutation type?
    Back
    Nonsense (produces a truncated protein )
  35. Front
    An insertion or deletion of a number of nucleotides NOT divisible by three causes what?
    Back
    A frameshift
  36. Front
    What is the protein-level consequence of a frameshift ?
    Back
    Every downstream codon is misread — almost always complete loss of function
  37. Front
    Which DNA polymerase activity provides real-time proofreading during replication?
    Back
    3′→5′ exonuclease activity
  38. Front
    E. coli 's raw polymerase error rate is 1 in 10⁷; what is the effective rate after proofreading and repair?
    Back
    1 in 10¹⁰–10¹¹
  39. Front
    Which suicide enzyme directly reverses O6-methylguanine by transferring the methyl group to its own cysteine?
    Back
    MGMT (O6-methylguanine DNA methyltransferase)
  40. Front
    What happens to MGMT after it repairs one O6-methylguanine lesion?
    Back
    It is permanently inactivated (a suicide enzyme )
  41. Front
    Which enzyme uses visible-light energy to directly break thymine dimers (photoreactivation)?
    Back
    Photolyase
  42. Front
    Is photolyase present in placental mammals (including humans)?
    Back
    No — it is absent in placental mammals (found in bacteria, yeast, non-mammalian vertebrates )
  43. Front
    Which repair pathway do humans rely on to remove thymine dimers , since they lack photolyase ?
    Back
    Nucleotide excision repair (NER)
  44. Front
    Which repair pathway handles small, non-helix-distorting lesions like uracil and 8-oxoguanine ?
    Back
    Base excision repair (BER)
  45. Front
    Which enzyme initiates BER by recognizing the wrong base and cleaving its N-glycosidic bond?
    Back
    A DNA glycosylase
  46. Front
    Which glycosylase removes 8-oxoguanine in base excision repair?
    Back
    OGG1
  47. Front
    In BER , which enzyme nicks the backbone at the AP site after the glycosylase acts?
    Back
    AP endonuclease
  48. Front
    Which repair pathway corrects large helix-distorting lesions like thymine dimers and bulky PAH/aflatoxin adducts ?
    Back
    Nucleotide excision repair (NER)
  49. Front
    In prokaryotic NER , which complex scans for the helix distortion?
    Back
    The UvrA-UvrB complex
  50. Front
    In prokaryotic NER , which protein makes the two incisions flanking the lesion?
    Back
    UvrC
  51. Front
    How long is the excised fragment in eukaryotic NER ?
    Back
    Roughly 25–30 nucleotides (vs ~12–13 in bacteria)
  52. Front
    Which autosomal recessive disease results from a defect in any NER gene (XPA–XPG)?
    Back
    Xeroderma pigmentosum (XP)
  53. Front
    What lesion accumulates in Xeroderma pigmentosum patients because they cannot repair it?
    Back
    UV-induced cyclobutane pyrimidine (thymine) dimers
  54. Front
    Which repair pathway scans freshly synthesized DNA for base-pair geometry errors that escaped proofreading?
    Back
    Mismatch repair (MMR)
  55. Front
    In E. coli MMR , how is the new (daughter) strand distinguished from the parental template?
    Back
    By methylation — the parental strand carries N6-methyladenine at GATC; the daughter strand is transiently unmethylated
  56. Front
    In E. coli MMR , which protein nicks the unmethylated daughter strand near the GATC site?
    Back
    MutH
  57. Front
    Name the human homologs of the mismatch repair proteins .
    Back
    MSH2, MSH6, MLH1, PMS2
  58. Front
    Failure of mismatch repair produces which phenotype at short tandem repeat sequences?
    Back
    Microsatellite instability
  59. Front
    Inherited loss of mismatch repair genes causes which hereditary cancer syndrome?
    Back
    Lynch syndrome (HNPCC)
  60. Front
    What fraction of all colorectal cancers is attributable to inherited MMR mutations ( Lynch syndrome )?
    Back
    3–5%
  61. Front
    What fraction of Lynch syndrome cases is explained by mutations in the human Mut-protein homologs?
    Back
    About 90%
  62. Front
    BRCA1 and BRCA2 mutations impair the repair of which type of DNA damage?
    Back
    Double-strand breaks (homologous recombination repair)
  63. Front
    What is the lifetime breast cancer risk for a woman carrying a BRCA1 mutation?
    Back
    55–65%
  64. Front
    What is the lifetime ovarian cancer risk for a BRCA1 carrier?
    Back
    40–45%
  65. Front
    Match the lesion: deaminated cytosine ( uracil ) is repaired by which pathway?
    Back
    Base excision repair (BER) , initiated by uracil-DNA glycosylase
  66. Front
    A codon change that swaps in an amino acid with SIMILAR properties (e.g., Lys→Arg) is which mutation subtype?
    Back
    Conservative missense
  67. Front
    What is the usual protein-level effect of a conservative missense mutation?
    Back
    Often mild or no change in function
  68. Front
    Conservative vs non-conservative missense: which substitutes a chemically SIMILAR amino acid and which substitutes one with DIFFERENT properties?
    Back
    Conservative = similar properties (often mild/no effect); non-conservative = different properties (usually impairs function)
  69. Front
    What kind of crosslinks do bifunctional alkylating agents create in DNA?
    Back
    Intra- or inter-strand crosslinks that physically trap the double helix
  70. Front
    Why are bifunctional (as opposed to monofunctional) alkylating agents especially damaging to the double helix?
    Back
    They alkylate two sites, forming intra- or inter-strand crosslinks that physically trap the two strands together
  71. Front
    Which enzyme seals the final nick as the common closing step of both base excision repair and nucleotide excision repair ?
    Back
    DNA ligase
  72. Front
    In base excision repair , what is the ordered enzyme cascade from lesion recognition to the sealed strand?
    Back
    DNA glycosylase → AP endonuclease → DNA polymerase (gap fill) → DNA ligase (seal)
  73. Front
    In nucleotide excision repair , after DNA polymerase fills the gap, which enzyme completes the pathway?
    Back
    DNA ligase (seals the nick)
  74. Front
    Besides collapsing into single-strand breaks , what two other consequences does an unrepaired AP site cause?
    Back
    It blocks transcription and stalls/causes errors in replication (no base to instruct the incoming nucleotide)
  75. Front
    Why does an AP site cause replication to stall or err?
    Back
    There is no base present to instruct (template) the incoming nucleotide
  76. Front
    At least how many overlapping DNA repair systems do cells run?
    Back
    Five
  77. Front
    Which DNA repair system is the FIFTH pathway, handling double-strand breaks via homologous recombination?
    Back
    Recombinational (homologous recombination) repair — the BRCA1/BRCA2 -dependent pathway
  78. Front
    Recombinational repair of double-strand breaks is coordinated by which two proteins whose loss escalates genomic instability?
    Back
    BRCA1 and BRCA2
  79. Front
    Which specific glycosylase initiates base excision repair of the uracil produced by cytosine deamination?
    Back
    Uracil-DNA glycosylase (UNG)
  80. Front
    In mismatch repair , which protein ( E. coli ) recognizes the mispaired bases or small insertion/deletion loop?
    Back
    MutS
  81. Front
    What two kinds of geometry errors does the mismatch repair system scan for in newly synthesized DNA?
    Back
    Mispaired bases (e.g., a G opposite a T) and small insertion/deletion loops
  82. Front
    What is the central challenge mismatch repair must solve to fix an error correctly?
    Back
    Strand discrimination — distinguishing the new (daughter) error-containing strand from the old (parental) template
  83. Front
    If translesion synthesis copies across an unrepaired UV thymine dimer , which mutation type typically accumulates at dipyrimidine sites?
    Back
    C→T transitions
  84. Front
    After MutH nicks the daughter strand in E. coli mismatch repair , which enzyme unwinds the DNA so the mismatch-containing segment can be removed?
    Back
    DNA helicase II (with exonucleases )
  85. Front
    Which repair pathway chemically reverses a lesion in place without excising or cutting any strand (e.g., MGMT , photolyase )?
    Back
    Direct repair

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