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Double-strand breaks from a radical commonly produced by DNA-damaging agents.

ABSTRACT: 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.

SUBMITTER: Taverna Porro ML

PROVIDER: S-EPMC4415041 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Double-strand breaks from a radical commonly produced by DNA-damaging agents.

Taverna Porro Marisa L ML Greenberg Marc M MM

Chemical research in toxicology 20150309 4

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 abs ...[more]

PMID: 25749510

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