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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Dynamic Processing of a Common Oxidative DNA Lesion by the First Two Enzymes of the Base Excision Repair Pathway.

Authors: Raper, Austin T; Maxwell, Brian A; Suo, Zucai

Published In J Mol Biol, (2021 03 05)

Abstract: Base excision repair (BER) is the primary pathway by which eukaryotic cells resolve single base damage. One common example of single base damage is 8-oxo-7,8-dihydro-2'-deoxoguanine (8-oxoG). High incidence and mutagenic potential of 8-oxoG necessitate rapid and efficient DNA repair. How BER enzymes coordinate their activities to resolve 8-oxoG damage while limiting cytotoxic BER intermediates from propagating genomic instability remains unclear. Here we use single-molecule Förster resonance energy transfer (smFRET) and ensemble-level techniques to characterize the activities and interactions of consecutive BER enzymes important for repair of 8-oxoG. In addition to characterizing the damage searching and processing mechanisms of human 8-oxoguanine glycosylase 1 (hOGG1), our data support the existence of a ternary complex between hOGG1, the damaged DNA substrate, and human AP endonuclease 1 (APE1). Our results indicate that hOGG1 is actively displaced from its abasic site containing product by protein-protein interactions with APE1 to ensure timely repair of damaged DNA.

PubMed ID: 33450252 Exiting the NIEHS site

MeSH Terms: 8-Hydroxy-2'-Deoxyguanosine/analogs & derivatives*; 8-Hydroxy-2'-Deoxyguanosine/chemistry; 8-Hydroxy-2'-Deoxyguanosine/metabolism; Binding Sites; DNA Damage; DNA Glycosylases/chemistry*; DNA Glycosylases/genetics; DNA Glycosylases/metabolism; DNA Repair*; DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry*; DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism; DNA/chemistry*; DNA/genetics; DNA/metabolism; Fluorescence Resonance Energy Transfer; Gene Expression; Genome, Human; Genomic Instability; Humans; Kinetics; Models, Molecular; Mutation; Nucleic Acid Conformation; Oxidation-Reduction; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Single Molecule Imaging; Substrate Specificity

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