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Updated: Jun 17, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions
Rachel Amouroux1, Anna Campalans, Bernd Epe
1CEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 route du Panorama, UMR217 F-92265 Fontenay aux Roses, France.
Abstract:
How DNA repair machineries detect and access, within the context of chromatin, lesions inducing little or no distortion of the DNA structure is a poorly understood process. Removal of oxidized bases is initiated by a DNA glycosylase that recognises and excises the damaged base, initiating the base excision repair (BER) pathway. We show that upon induction of 8-oxoguanine, a mutagenic product of guanine oxidation, the mammalian 8-oxoguanine DNA glycosylase OGG1 is recruited together with other proteins involved in BER to euchromatin regions rich in RNA and RNA polymerase II and completely excluded from heterochromatin. The underlying mechanism does not require direct interaction of the protein with the oxidized base, however, the release of the protein from the chromatin fraction requires completion of repair. Inducing chromatin compaction by sucrose results in a complete but reversible inhibition of the in vivo repair of 8-oxoguanine. We conclude that after induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions, suggesting preferential repair of active chromosome regions.
Insights
Mammalian 8-oxoguanine DNA glycosylase (OGG1) is recruited to open chromatin regions to repair oxidative DNA damage. DNA repair preferentially occurs in active chromosome regions, not condensed heterochromatin.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA repair mechanisms are crucial for maintaining genomic stability.
- Understanding how DNA repair proteins access damaged DNA within chromatin is essential.
- Oxidative DNA damage, such as 8-oxoguanine, is mutagenic and requires efficient repair.
Purpose of the Study:
- To investigate the recruitment and mechanism of DNA repair proteins to oxidative DNA lesions.
- To determine the role of chromatin structure in DNA repair accessibility.
- To elucidate the preferential repair of DNA damage in specific chromatin regions.
Main Methods:
- Induction of 8-oxoguanine in mammalian cells.
- Chromatin fractionation and protein recruitment analysis.
- Assessment of DNA repair inhibition by chromatin compaction.
Main Results:
- Mammalian 8-oxoguanine DNA glycosylase (OGG1) and base excision repair (BER) proteins are recruited to euchromatin, rich in RNA and RNA polymerase II.
- OGG1 recruitment does not require direct interaction with the oxidized base.
- Chromatin compaction by sucrose reversibly inhibits in vivo 8-oxoguanine repair.
- OGG1 release from chromatin requires completion of the repair process.
Conclusions:
- DNA glycosylase is actively recruited to open chromatin regions following oxidative DNA damage.
- The base excision repair (BER) machinery gains access to lesions in euchromatin.
- DNA repair is preferentially targeted to active chromosome regions, suggesting a link between transcription and repair.
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