Chromatin recruitment of OGG1 requires cohesin and mediator and is essential for efficient 8-oxoG removal

One of the most abundant DNA lesions induced by oxidative stress is the highly mutagenic 8-oxoguanine (8-oxoG), which is specifically recognized by 8-oxoguanine DNA glycosylase 1 (OGG1) to initiate its repair. How DNA glycosylases find small non-helix-distorting DNA lesions amongst millions of bases...

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Bibliographic Details
Published in:Nucleic acids research 2020-09, Vol.48 (16), p.9082-9097
Main Authors: Lebraud, Emilie, Pinna, Guillaume, Siberchicot, Capucine, Depagne, Jordane, Busso, Didier, Fantini, Damiano, Irbah, Lamya, Robeska, Elena, Kratassiouk, Gueorgui, Ravanat, Jean-Luc, Epe, Bernd, Radicella, J Pablo, Campalans, Anna
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Cell Cycle Proteins - genetics
Cellular Biology
Chromatin - genetics
Chromosomal Proteins, Non-Histone - genetics
Cohesins
DNA Glycosylases - genetics
DNA Repair - genetics
Euchromatin - genetics
Genome Integrity, Repair and
Genomic Instability - genetics
Guanine - analogs & derivatives
Guanine - metabolism
HeLa Cells
Humans
Life Sciences
Molecular biology
Oxidative Stress - genetics
RNA, Small Interfering - genetics
Subcellular Processes
Transfection
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Summary:One of the most abundant DNA lesions induced by oxidative stress is the highly mutagenic 8-oxoguanine (8-oxoG), which is specifically recognized by 8-oxoguanine DNA glycosylase 1 (OGG1) to initiate its repair. How DNA glycosylases find small non-helix-distorting DNA lesions amongst millions of bases packaged in the chromatin-based architecture of the genome remains an open question. Here, we used a high-throughput siRNA screening to identify factors involved in the recognition of 8-oxoG by OGG1. We show that cohesin and mediator subunits are required for re-localization of OGG1 and other base excision repair factors to chromatin upon oxidative stress. The association of OGG1 with euchromatin is necessary for the removal of 8-oxoG. Mediator subunits CDK8 and MED12 bind to chromatin and interact with OGG1 in response to oxidative stress, suggesting they participate in the recruitment of the DNA glycosylase. The oxidative stress-induced association between the cohesin and mediator complexes and OGG1 reveals an unsuspected function of those complexes in the maintenance of genomic stability.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkaa611