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Visible Light-Induced Radical Mediated DNA Damage
Amelia C McCue1, Whitney M Moreau2, Thomas A Shell3
1Department of Chemistry, Saint Anselm College, Manchester, NH.
Photochemistry and Photobiology
|January 30, 2018
Summary
Alkylcobalamins activated by green light generate radicals that damage DNA. A modified compound with a DNA-binding moiety significantly enhances this DNA cleavage effect.
Area of Science:
- Photochemistry
- Molecular Biology
- Biochemistry
Background:
- Light-responsive compounds offer precise spatial and temporal control in biological systems.
- Alkylcobalamins illuminated with green light (>500 nm) generate carbon-centered radicals capable of inducing DNA damage.
- Existing DNA-damaging agents often require damaging ultraviolet light, which can harm nucleotide bases.
Purpose of the Study:
- To investigate the efficacy of alkylcobalamins as light-activated agents for DNA strand scission.
- To explore the mechanism of DNA damage induced by green light-activated alkylcobalamins.
- To enhance DNA cleavage efficiency using alkylcobalamins conjugated with DNA-binding moieties.
Main Methods:
- Illumination of alkylcobalamins with green light (>500 nm).
- Assessment of DNA strand scission using gel mobility assays.
- Radical trapping studies to confirm the generation of carbon-centered radicals.
- Synthesis and evaluation of spermine-conjugated alkylcobalamins for improved DNA cleavage.
Main Results:
- Green light illumination of methylcobalamin induced DNA strand scission.
- The cleavage mechanism involves the generation of carbon-centered radicals.
- Conjugation of spermine to alkylcobalamin enhanced DNA cleavage efficacy by tenfold compared to methylcobalamin.
Conclusions:
- Alkylcobalamins are advantageous for light-induced DNA strand scission due to activation by non-damaging green light wavelengths.
- The generation of carbon-centered radicals is the primary mechanism for DNA cleavage.
- Spermine conjugation significantly improves the efficiency of light-activated DNA cleavage, offering a promising tool for polynucleotide studies.
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