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7.S: Mutation and Repair of DNA (Summary)

  • Page ID
    348
  • Summary: Causes of Transitions and Transversions

    Table 7.1 lists several causes of mutations in DNA, including mutagens as well as mutator strains in bacteria. Note that some of these mutations lead to mispairing (substitutions), others lead to distortions of the helix, and some lead to both. Transitions can be generated both by damage to the DNA and by misincorporation during replication. Transversions occur primarily by misincorporation during replication. The frequency of such errors is greatly increased in mutator strains, e.g. lacking a proofreading function in the replicative DNA polymerase. Also, after a bacterial cell has sustained sufficient damage to induce the SOS response, the DNA polymerase shifts into a an error-prone mode of replication. This can also be a source of mutant alleles.


    Table. 7.1. Summary of effects of various agents that alter DNA sequences (mutagens and mutator genes)
    Agent (mutagen, etc.) Example Result
    Nucleotide analogs BrdUTP transitions, e.g. A:T to G:C
    Oxidizing agents nitrous acid transitions, e.g. C:G to T:A
    Alkylating agents nitrosoguanidine transitions, e.g. G:C to A:T
    Frameshift mutagens Benz(a)pyrene deletions (short)
    Ionizing radiation X-rays, g-rays breaks and deletions (large)
    UV UV, 260 nm Y-dimers, block replication
    Misincorporation:
    Altered DNA Pol III mutD=dnaQ; e subunit of DNA PolIII transitions, transversions and frameshifts in mutant strains
    Error-prone repair Need UmuC, UmuD, DNA PolIII transitions and transversions in wild-type during SOS
    Other mutator genes mutM, mutT, mutY transversions in the mutant strains

    Additional Readings

    • Friedberg, E. C., Walker, G. C., and Siede, W. (1995) DNA repair and mutagenesis, ASM Press, Washington, D.C.
    • Kornberg, A. and Baker, T. (1992) DNA Replication, 2nd Edition, W. H. Freeman and Company, New York.
    • Zakian, V. (1995) ATM-related genes: What do they tell us about functions of the human gene? Cell 82: 685-687.
    • Kolodner, R. (1996) Biochemistry and genetics of eukaryotic mismatch repair. Genes & Development10:1433-1442.
    • Sutton MD, Smith BT, Godoy VG, Walker GC. (2000) The SOS response: recent insights into umuDC-dependent mutagenesis and DNA damage tolerance.Annu Rev Genet34:479-497.
    • De Laat, W. L., Jaspers, N. C. J. and Hoeijmakers, J. H. J. (1999) Molecular mechanism of nucleotide excision repair. Genes & Development13: 768-785. This review focuses on nucleotide excision repair in mammals.