Exocyclic adducts to DNA bases are formed as a consequence of exposure to certain environmental carcinogens as well as inflammation and lipid peroxidation (LPO). Complex family of LPO products gives rise to a variety of DNA adducts, which can be grouped in two classes: (i) small etheno-type adducts of strong mutagenic potential, and (ii) bulky, propano-type adducts, which block replication and transcription, and are lethal lesions. Etheno-DNA adducts are removed from the DNA by base excision repair (BER), AlkB and nucleotide incision repair enzymes (NIR), while substituted propano-type lesions by nucleotide excision repair (NER) and homologous recombination (HR). Changes of the level and activity of several enzymes removing exocyclic adducts from the DNA was reported during carcinogenesis. Also several beyond repair functions of these enzymes, which participate in regulation of cell proliferation and growth, as well as RNA processing was recently described. In addition, adducts of LPO products to proteins was reported during aging and age-related diseases. The paper summarizes pathways for exocyclic adducts removal and describes how proteins involved in repair of these adducts can modify pathological states of the organism.
Keywords: AlkB; BER; Enzyme modification; Etheno-DNA adducts; Homologous recombination; Lipid peroxidation; NER; NIR; Propano-DNA adducts; RNA processing.
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