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(PP347) Processing of 8-oxoguanine within close proximity to a DNA single strand break.
Parsons, Jason*,1, Dianov, Grigory1, 1 Radiation and Genome Stability Unit, Didcot, Oxfordshire, UK
ABSTRACT- Ionizing radiation, oxidative stress and endogenous DNA damage processing can result in clustered lesions that are present within one or two helical turns of the DNA. Consequently, the formation of multiply damaged sites in DNA may include 8-oxoguanine (8-oxoG) lesions in close proximity to single-strand breaks on the same DNA strand that may be potentially deleterious to the cell. This study examines the processing of 8-oxoG lesions when present near the 3′-end of a DNA single-strand break. Using fractionated human cell extracts and purified base excision repair proteins, we isolated the major activities involved in the repair of DNA substrates containing 3′-end 8-oxoG and also analysed the repair of 8-oxoG when placed in site-specific positions 5′-upstream to the single-strand break. We find that the repair pathway chosen for the excision of 8-oxoguanine is dependent on the position of the lesion relative to the strand break. Therefore, the repair of clustered lesions containing 8-oxoG and single-strand breaks involves several distinct DNA repair enzymes.
Key words: DNA repair, 8-oxoguanine, single strand break, base excision repair
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