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

Abstract

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.