Double-strand breaks from a radical commonly produced by DNA-damaging agents.
Double-strand breaks are widely accepted to be the most toxic form of DNA damage. Molecules that produce double-strand breaks via a single chemical event are typically very cytotoxic and far less common than those that form single-strand breaks. It was recently reported that a commonly formed C4'-radical produces double-strand breaks under aerobic conditions. Experiments described herein indicate that a peroxyl radical initiates strand damage on the complementary strand via C4'-hydrogen atom abstraction. Inferential evidence suggests that a C3'-peroxyl radical induces complementary strand damage more efficiently than does a C4'-peroxyl radical. Complementary strand hydrogen atom abstraction by the peroxyl radical is efficiently quenched by thiols. This mechanism could contribute to the higher than expected yield of double-strand breaks produced by ionizing radiation.
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Marisa L
ML
Taverna Porro
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Marc M
MM
Greenberg
D004249:DNA Damage; D005609:Free Radicals; D007554:Isotopes
D005609:Free Radicals; D007554:Isotopes