Spatio-temporal dynamics of the DNA glycosylase OGG1 in finding and processing 8-oxoguanine

• Published in: DNA repair 2023-09, Vol.129, p.103550-103550, Article 103550
• Main Authors: Cintori, Luana, Di Guilmi, Anne-Marie, Canitrot, Yvan, Huet, Sebastien, Campalans, Anna
• Format: Article
• Language: English
• Subjects: 8-oxoguanine; BER; DNA repair; Genetics; Life Sciences; Microscopy; OGG1; Single-molecule
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2023.103550

OGG1 is the DNA glycosylase responsible for the removal of the oxidative lesion 8-oxoguanine (8-oxoG) from DNA. The recognition of this lesion by OGG1 is a complex process that involves scanning the DNA for the presence of 8-oxoG, followed by recognition and lesion removal. Structural data have shown that OGG1 evolves through different stages of conformation onto the DNA, corresponding to elementary steps of the 8-oxoG recognition and extrusion from the double helix. Single-molecule studies of OGG1 on naked DNA have shown that OGG1 slides in persistent contact with the DNA, displaying different binding states probably corresponding to the different conformation stages. However, in cells, the DNA is not naked and OGG1 has to navigate into a complex and highly crowded environment within the nucleus. To ensure rapid detection of 8-oxoG, OGG1 alternates between 3D diffusion and sliding along the DNA. This process is regulated by the local chromatin state but also by protein co-factors that could facilitate the detection of oxidized lesions. We will review here the different methods that have been used over the last years to better understand how OGG1 detects and process 8-oxoG lesions. •Spatio-temporal dynamics of OGG1 along naked DNA at the single molecule level•Nuclear dynamics of OGG1 upon induction of 8-oxoG at the global genome level•Real-time recruitment kinetics of OGG1 to 8-oxoG induced by laser micro-irradiation•Chemoptogenetic tools to precisely target the induction of 8-oxoG at specific genomic regions