Processing of clustered DNA damage generates additional double-strand breaks in mammalian cells post-irradiation

AUTOR(ES)

Gulston, Melanie

FONTE

Oxford University Press

RESUMO

Clustered DNA damage sites, in which two or more lesions are formed within a few helical turns of the DNA after passage of a single radiation track, are signatures of DNA modifications induced by ionizing radiation in mammalian cells. Mutant hamster cells (xrs-5), deficient in non-homologous end joining (NHEJ), were irradiated at 37°C to determine whether any additional double-strand breaks (DSBs) are formed during processing of γ-radiation-induced DNA clustered damage sites. A class of non-DSB clustered DNA damage, corresponding to ∼30% of the initial yield of DSBs, is converted into DSBs reflecting an artefact of preparation of genomic DNA for pulsed field gel electrophoresis. These clusters are removed within 4 min in both NHEJ-deficient and wild-type CHO cells. In xrs-5 cells, a proportion of non-DSB clustered DNA damage, representing ∼10% of the total yield of non-DSB clustered DNA damage sites, are also converted into DSBs within ∼30 min post-γ but not post-α irradiation through cellular processing at 37°C. That the majority of radiation-induced non-DSB clustered DNA damage sites are resistant to conversion into DSBs may be biologically significant at environmental levels of radiation exposure, as a non-DSB clustered damage site rather than a DSB, which only constitutes a minor proportion, is more likely to be induced in irradiated cells.

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