DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism
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We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5′ and 3′ ends of the repaired gene. During a two-week period after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes further modifies methylation of the repaired DNA. Subsequently, the repaired genes display stable but diverse methylation profiles. These profiles govern the levels of expression in each clone. Our data argue that DNA methylation and chromatin remodelling induced by HR may be a source of permanent variation of gene expression in somatic cells.
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ROS are able to induce DNA hypermethylation, with potential consequences on tumor phenotype when promoter regions of tumor suppressor genes are involved.
“However, ROS are able to induce DNA hypermethylation as well, with potential consequences on tumor phenotype when promoter regions of tumor suppressor genes are involved43–45.”
From ROS in cancer therapy: the bright side of the moon (2020) · cites this paper as [44]
The Results section (page unavailable) reports hypermethylation of a targeted GFP locus after DNA double-strand-break repair, with differences in GFP expression. The paper does not show that ROS caused the hypermethylation or examine tumor-suppressor promoters or tumor phenotype. (LLM, conf=0.84)
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- Authors
- Russo, G., Landi, R., Pezone, A., Morano, A., Zuchegna, C., Romano, A., Muller, M. T., Gottesman, M. E., Porcellini, A., & Avvedimento, E. V.
- Affiliations
- Institute for Experimental Endocrinology and Oncology (IT)
- University of Naples Federico II (IT)
- TopoGEN (United States) (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Porcellini, Antonio
- Avvedimento, Enrico V.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-09-15
- Volume
- 6
- Issue
- 1
- Pages
- 33222-33222
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5024116
- OpenAlex
- W2520333406
- Cited by
- 86
- References
- 34
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 11 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 12 · 2018: 4 · 2017: 8
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Fondazione Umberto Veronesi
- Associazione Italiana per la Ricerca sul Cancro (16983)
- National Institutes of Health
- National Institute of General Medical Sciences (R43GM113286)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, homologous recombination, DNA repair, chromatin structure, histone H3 methylation, base excision repair, epigenetic variation, gene expression variation, somatic cells
- MeSH terms
- Alleles, Chromatin, DNA Damage, DNA Repair, Histones, Humans, Methylation, DNA Methylation
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