Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?

International Journal of Molecular Sciences

Ostiane D’Augustin¹  JuanPablo Radicella¹  Anna Campalans¹  Sébastien Huet² 

[1] Institute of Cellular and Molecular Radiobiology, Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Université de Paris, 18 route du Panorama, F-92265 Fontenay-aux-Roses, France;Univ Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes)-UMR 6290, BIOSIT-UMS3480, F-35000 Rennes, France;

关键词: OGG1;    8-oxoG;    DNA repair;    base excision repair;    search mechanism;   

DOI  :  10.3390/ijms21218360

来源: DOAJ

【 摘 要 】

The most frequent DNA lesion resulting from an oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoG). 8-oxoG is a premutagenic base modification due to its capacity to pair with adenine. Thus, the repair of 8-oxoG is critical for the preservation of the genetic information. Nowadays, 8-oxoG is also considered as an oxidative stress-sensor with a putative role in transcription regulation. In mammalian cells, the modified base is excised by the 8-oxoguanine DNA glycosylase (OGG1), initiating the base excision repair (BER) pathway. OGG1 confronts the massive challenge that is finding rare occurrences of 8-oxoG among a million-fold excess of normal guanines. Here, we review the current knowledge on the search and discrimination mechanisms employed by OGG1 to find its substrate in the genome. While there is considerable data from in vitro experiments, much less is known on how OGG1 is recruited to chromatin and scans the genome within the cellular nucleus. Based on what is known of the strategies used by proteins searching for rare genomic targets, we discuss the possible scenarios allowing the efficient detection of 8-oxoG by OGG1.

【 授权许可】

Unknown