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Study of ultraviolet light-induced DNA damage and repair: the role of the (6-4) photoproduct

Thesis/Dissertation ·
OSTI ID:5005744
Ultraviolet light induces lethal, mutagenic, and carcinogenic effects to cells. These effects are a result of the induction of photoproducts in the cellular DNA. One class of photoproducts was found as alkaline labile lesions in DNA, and it was proposed that such lesions were precursor products to the 6,4'-(pyrimidin-2'-one)-pyrimidine class of photoproducts that have been previously shown to occur in UV light-irradiated DNA. Using a series of dinucleotide compounds, the precursor compounds were isolated, and were demonstrated to be alkaline labile. These products were named the UV light-induced pyrimidine-pyrimidone (6-4) photoproducts, and their chemistry of formation in dinucleotides and DNA was studied. The formation of these photoproducts under conditions of chemical photosensitization was also measured. The most abundant of the (6-4) photoproducts is the thymine-cytosine (6-4) product, and the molecular structure of this compounds was determined by the use of infrared spectroscopy, proton NMR, and mass spectroscopy. The (6-4) products have been recently shown to be the major UV light-induced premutagenic lesions in E. coli. In E. coli, the repair of the (6-4) products is under the control of the uvrABC excision pathway. The rate of removal of (6-4) products was measured in a series of human cells lines. The rate of removal of (6-4) products from the DNA of a xeroderma pigmentosum complementation group A cell line was nearly that of the normal cells, yet these cells are unable to excise cyclobutane pyrimidine dimers. These results suggest that the removal of cyclobutane pyrimidine dimers and (6-4) products may be controlled by separate enzymatic pathways.
Research Organization:
Harvard Univ., Boston, MA (USA)
OSTI ID:
5005744
Country of Publication:
United States
Language:
English

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Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DNA
DNA REPAIR
ELECTROMAGNETIC RADIATION
ENZYME ACTIVITY
ESCHERICHIA COLI
EXTREME ULTRAVIOLET RADIATION
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PYRIMIDINE DIMERS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RECOVERY
REPAIR
ULTRAVIOLET RADIATION