摘要：Ionizing radiation induces a wide variety of modifications to purine and pyrimidine residues. The exocyclic methyl group of thymine does not escape oxidative damage. Any 5-hydroperoxymethyluracil produced is spontaneously decomposed to form 5-formyluracil (5-foU) and 5-hydroxymethyluracil. The yield of 5-foU by ionizing radiation is roughly the same as that of 8-oxoguanine. 5-foU is a potential mutagenic damage in vitro and in vivo . Mammalian cells have an activity that removes 5-foU from X-irradiated DNA. Furthermore, the Nth, Nei and MutM proteins of E. coli have DNA glycosylase/AP lyase activities that recognize and remove 5-foU in DNA. The mutation frequency of 5-foU-containing plasmid increases when replicated in E. coli nthneimutMalkA . Single mutations in the nth , nei or mutM gene do not affect the mutation frequency. Therefore, these gene products are likely backup enzymes used to repair 5-foU in DNA. Furthermore, the human hNTH1 enzyme, a homologue of E. coli Nth, is found to have similar DNA glycosylase activity to that of the Nth protein.
关键词：Ionizing radiation; Reactive oxygen species; Oxidative base damage; 5-Formyluracil; DNA glycosylase; Mutation
