Lidstrom:UV Mutagenesis: Difference between revisions

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*[http://www.photobiology.info/UV-Muta.html UV Radiation and Spontaneous Mutagenesis]: summary by Kendric C. Smith, Emeritus Professor, Radiation Oncology (Radiation Biology), Stanford University School of Medicine
*[http://www.photobiology.info/UV-Muta.html UV Radiation and Spontaneous Mutagenesis]: summary by Kendric C. Smith, Emeritus Professor, Radiation Oncology (Radiation Biology), Stanford University School of Medicine
** Discusses repair mechanisms a lot.  
** Discusses repair mechanisms a lot.  
**"G:C -> A:T transitions predominate after UV irradiation. In E. coli the (6-4)-photoproduct may be more important for mutagenesis, while the pyrimidine dimer may be more important in mammalian cells. In human cells, mutations occur at the C of a TC, CT, or CC pyrimidine dimer, but not at TT dimers, and also occur at the C of TC and CC (6-4)-adducts (reviewed by Brash, 1988)."
** UV radiation produces a preponderance of alterations in the pyrimidines, and the large majority of these products involve the linking of two adjacent pyrimidines
** "Therefore, as with survival, no one UV-radiation-induced lesion can be assigned as the one and only mutagenic lesion. Under certain experimental conditions, and in certain base sequences within a gene, pyrimidine dimers can be the most important mutagenic lesions, however, under other experimental conditions, and at other base sequences (e.g., CC sites), the (6-4)-adduct can be the most important. Furthermore, purine photoproducts have been identified, and have been implicated in mutagenesis (reviewed in Brash, 1988). Therefore, statements about the relative importance of different photoproducts in lethality and mutagenesis must be assessed on an experiment by experiment basis. "
**"G:C -> A:T transitions predominate after UV irradiation.  
***In E. coli the (6-4)-photoproduct may be more important for mutagenesis, while the pyrimidine dimer may be more important in mammalian cells. In human cells, mutations occur at the C of a TC, CT, or CC pyrimidine dimer, but not at TT dimers, and also occur at the C of TC and CC (6-4)-adducts (reviewed by Brash, 1988)."
** UV-radiation-induced mutations show 2-hit kinetics at high doses
*** i.e., they are produced as a function of the square of the dose
** While UV irradiation does not produce DNA double-strand breaks directly, they can be formed as a consequence of the inefficient repair of overlapping excision gaps, and of overlapping daughter-strand gaps
** The formation of DNA-protein cross-links has been shown to be of significance in the killing of E. coli
** In general, UV irradiation produces mutations along a gene in a non-random manner, i.e., mutations are observed at certain base pairs more frequently than at others

Revision as of 07:47, 1 July 2014

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  • UV Radiation and Spontaneous Mutagenesis: summary by Kendric C. Smith, Emeritus Professor, Radiation Oncology (Radiation Biology), Stanford University School of Medicine
    • Discusses repair mechanisms a lot.
    • UV radiation produces a preponderance of alterations in the pyrimidines, and the large majority of these products involve the linking of two adjacent pyrimidines
    • "G:C -> A:T transitions predominate after UV irradiation.
      • In E. coli the (6-4)-photoproduct may be more important for mutagenesis, while the pyrimidine dimer may be more important in mammalian cells. In human cells, mutations occur at the C of a TC, CT, or CC pyrimidine dimer, but not at TT dimers, and also occur at the C of TC and CC (6-4)-adducts (reviewed by Brash, 1988)."
    • UV-radiation-induced mutations show 2-hit kinetics at high doses
      • i.e., they are produced as a function of the square of the dose
    • While UV irradiation does not produce DNA double-strand breaks directly, they can be formed as a consequence of the inefficient repair of overlapping excision gaps, and of overlapping daughter-strand gaps
    • The formation of DNA-protein cross-links has been shown to be of significance in the killing of E. coli
    • In general, UV irradiation produces mutations along a gene in a non-random manner, i.e., mutations are observed at certain base pairs more frequently than at others
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