Lipid peroxidation in face of DNA damage, DNA repair and other cellular processes


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Abstract

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.HighlightsLipid peroxidation (LPO) generates reactive aldehydes which form adducts to DNA and proteins.Small etheno adducts to DNA bases are repaired by BER, AlkB and NIR, while bulky adducts by NER and recombination.Modulation of etheno adducts repair occurs in patients with lung and colon cancer.LPO products disrupt balance in DNA repair, which increases genomic instability.Additional functions of DNA repair proteins regulate transcription, translation and signal transduction.

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