ArticleNucleic acids research2012
GADD45α inhibition of DNMT1 dependent DNA methylation during homology directed DNA repair.
Article in Nucleic acids research, 2012. 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, 44 citations in OpenAlex.
- Translational potential of GADD45α: biomarker and therapeutic target in age-associated neurodegeneration and longevity.Biogerontology · 2025Review
- Exploring the molecular and functional cellular response to hydrazine via transcriptomics and DNA repair mutant cell lines.Environmental and molecular mutagenesis · 2022Article
- Gadd45 in DNA Demethylation and DNA Repair.Advances in experimental medicine and biology · 2022Article
- GADD45A is a protective modifier of neurogenic skeletal muscle atrophy.JCI insight · 2021Article
- High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites.Nature communications · 2021Article
- DNA methyltransferases in hematological malignancies.Journal of genetics and genomics = Yi chuan xue bao · 2020Review
- Methylation of the Suppressor GeneBiomolecules · 2020Article
- Non-homologous end joining induced alterations in DNA methylation: A source of permanent epigenetic change.Oncotarget · 2017Article
- DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism.Scientific reports · 2016Article
- Article
- Chromatin modifications during repair of environmental exposure-induced DNA damage: a potential mechanism for stable epigenetic alterations.Environmental and molecular mutagenesis · 2014Review
- Beyond transcriptional silencing: is methylcytosine a widely conserved eukaryotic DNA elimination mechanism?BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Article
- DNA DSB repair pathway choice: an orchestrated handover mechanism.The British journal of radiology · 2014Review
- Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene.Nucleic acids research · 2014Article
- Article
- The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance.Cell cycle (Georgetown, Tex.) · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
In this work, we examine regulation of DNA methyltransferase 1 (DNMT1) by the DNA damage inducible protein, GADD45α. We used a system to induce homologous recombination (HR) at a unique double-strand DNA break in a GFP reporter in mammalian cells. After HR, the repaired DNA is hypermethylated in recombinant clones showing low GFP expression (HR-L expressor class), while in high expressor recombinants (HR-H clones) previous methylation patterns are erased. GADD45α, which is transiently induced by double-strand breaks, binds to chromatin undergoing HR repair. Ectopic overexpression of GADD45α during repair increases the HR-H fraction of cells (hypomethylated repaired DNA), without altering the recombination frequency. Conversely, silencing of GADD45α increases methylation of the recombined segment and amplifies the HR-L expressor (hypermethylated) population. GADD45α specifically interacts with the catalytic site of DNMT1 and inhibits methylation activity in vitro. We propose that double-strand DNA damage and the resulting HR process involves precise, strand selected DNA methylation by DNMT1 that is regulated by GADD45α. Since GADD45α binds with high avidity to hemimethylated DNA intermediates, it may also provide a barrier to spreading of methylation during or after HR repair.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.