DNA mutation & repair part 1

  1. types of chemical mutagens
    • deaminating agents
    • alkylating agents
    • intercalating agents
  2. A certain amount of base __ occurs spontaneously in genomic DNA molecules.
    • deamination (removal of an amino group)
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  3. Rate of deamination is increased by some compounds such as __
    • nitrous acid (deaminates adenine, cytosine, and guanine)
    • sodium bisulfite (acts only on cytosine)
  4. Guanine deaminates into  __
    xanthine, which blocks replication (not mutagenic)
  5. Adenine deaminates into  __
    hypoxanthine (pairs with C)

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  6. Cytosine deaminates into __
    uracil (pairs with A)
  7. Deamination of __ results in point mutations when __
    A & C; the template strand is copied

    (since hypoxanthine pairs with C & uracil pairs with A)
  8. Which base cannot deaminate?
    thymine (because there is no amine group)
  9. __ agents give rise to point mutations
    Alkylating (by adding methyl and ethyl)
  10. Compounds such as Ethylmethane sulfonate (EMS) & methylating agents (such as methyl halides) are methylations that often result in __
    modified nucleotides with altered base pairing properties that lead to point mutations
  11. Some alkylations block replication by forming __, or the added __ groups prevent progress of the replication complex.
    • cross-links between the 2 strands of DNA;
    • large alkyl
  12. __ agents are usually associated with insertion or deletion mutations
  13. Ethidium bromide and other intercalating agents are flat molecules that can __
    slip between base pairs in the double helix, slightly unwinding the helix & hence, increasing the distance between adjacent base pairs (can affect the # of bases)

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  14. types of physical mutagens
    • UV radiation
    • ionizing radiation
    • heat
  15. UV radiation of wavelength 260nm induces __ of adjacent pyrimidine bases especially if these are both __ resulting in a __
    dimerization; thymines; cyclobutyl dimer

    (Other pyrimidine combos also form dimers - order of frequency: 5'-CT-3', 5'-TC-3', 5'-CC-3')
  16. UV-induced dimerization results in __
    DNA polymerase stalling when it reaches the dimers. A deletion mutation occurs when the modified strand is copied.
  17. A type of UV-induced base dimer is the photoproduct (6-4) lesion, in which __
    carbons number 4 & 6 of adjacent pyrimidines become covalently linked
  18. UV-induced base dimer (photo)
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  19. Ionization radiation may cause __
    • point mutations
    • insertion and/or deletion
    • double strand break

    Severe forms of DNA damage blocks the subsequent replication of the genome.
  20. Some types of ionization radiation act directly on DNA, other act indirectly by stimulating __
    the formation of reactive molecules such as peroxides in the cell
  21. Oxidation of guanine results in __
    Guanine turning into oxoG, which pairs with C and also with A. 

    Base pairing with A → transversion

    (ionizing radiation)
  22. clastogenic agents
    agents that cause double strand break

    examples: ionizing radiation and drugs such as bleomycin
  23. Heat enhances the water-induced __. This occurs more frequently with purines than with pyrimidines and results in an __
    • cleavage/hydrolysis of the b-N-glycosidic bond that attaches the base to the sugar component of the nucleotide;
    • AP (apurinic/apyrimidinic) site, or baseless site

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  24. the effect of heat-induced hydrolysis on double-stranded DNA
    • The sugar-phosphate is left unstable and rapidly degrades, leaving a gap
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  25. Is heat-induced hydrolysis normally mutagenic?
    no. Since the DNA molecule is double stranded, cells have effective systems for repairing gaps.
  26. silent mutation
    • has no effect on the coding function. e.g. causing no change in the coded amino acids or level of expression of a gene
    • occur in intergenic DNA and in the noncoding components of genes and gene related sequences

    In other words, some 98.5% of the human genome can be mutated without a significant effect.
  27. synonymous mutation
    • The new codon specifies the same amino acid as the unmutated codon (is a form of silent mutation)
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  28. nonsynonomous mutation
    • The mutation alters the codon so that is specifies a different amino acid (missense mutation)
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  29. nonsense mutation
    • The mutation may convert a codon that specifies an amino acid into a termination codon. It usually has a drastic effect on the function.
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  30. read through mutation
    • The mutation converts a termination codon into a codon specifying an amino acid, resulting in protein extension
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Card Set
DNA mutation & repair part 1
Week 6