ArticleProceedings of the National Academy of Sciences of the United States of America2020
Ligand-induced gene activation is associated with oxidative genome damage whose repair is required for transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Involvement of the DNA Demethylase Thymine DNA Glycosylase in Anticancer Drug Resistance.Biomolecules & therapeutics · 2025Article
- Strand-specific quantification of 8-oxo-dG and apurinic sites via Ligation-Dependent Probe Amplification (LPA).Redox biology · 2025Article
- Inflammation via JAK-STAT/HIF-1α Drives Metabolic Changes in Pentose Phosphate Pathway and Glycolysis That Support Aortic Valve Cell Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- ADP-ribosylation of NuMA promotes DNA single-strand break repair and transcription.Cell reports · 2025Article
- Curcumin-encapsulated exosomes in bisphosphonate-modified hydrogel microspheres promote bone repair through macrophage polarization and DNA damage mitigation.Materials today. Bio · 2025Article
- To Break or Not to Break: The Role of TOP2B in Transcription.International journal of molecular sciences · 2023Review
- ERK1/2-RSK regulation of oestrogen homeostasis.The FEBS journal · 2023Review
- The Intertwined Role of 8-oxodG and G4 in Transcription Regulation.International journal of molecular sciences · 2023Review
- 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification.Experimental & molecular medicine · 2022Review
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- Regulation of GC box activity by 8-oxoguanine.Redox biology · 2021Article
- Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in theInternational journal of molecular sciences · 2021Article
- Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin.Nucleic acids research · 2021Article
- Oxidative Modifications of RNA and Its Potential Roles in Biosystem.Frontiers in molecular biosciences · 2021Review
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Among several reversible epigenetic changes occurring during transcriptional activation, only demethylation of histones and cytosine-phosphate-guanines (CpGs) in gene promoters and other regulatory regions by specific demethylase(s) generates reactive oxygen species (ROS), which oxidize DNA and other cellular components. Here, we show induction of oxidized bases and single-strand breaks (SSBs), but not direct double-strand breaks (DSBs), in the genome during gene activation by ligands of the nuclear receptor superfamily. We observed that these damages were preferentially repaired in promoters via the base excision repair (BER)/single-strand break repair (SSBR) pathway. Interestingly, BER/SSBR inhibition suppressed gene activation. Constitutive association of demethylases with BER/SSBR proteins in multiprotein complexes underscores the coordination of histone/DNA demethylation and genome repair during gene activation. However, ligand-independent transcriptional activation occurring during heat shock (HS) induction is associated with the generation of DSBs, the repair of which is likewise essential for the activation of HS-responsive genes. These observations suggest that the repair of distinct damages induced during diverse transcriptional activation is a universal prerequisite for transcription initiation. Because of limited investigation of demethylation-induced genome damage during transcription, this study suggests that the extent of oxidative genome damage resulting from various cellular processes is substantially underestimated.
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Registered trials
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