ArticleGenes & development2017
Regulation of DNA demethylation by the XPC DNA repair complex in somatic and pluripotent stem cells.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Increased DNA damage of adipose tissue-derived mesenchymal stem cells under inflammatory conditions.Heliyon · 2024Article
- Single-molecule analysis of purified proteins and nuclear extracts: Insights from 8-oxoguanine glycosylase 1.DNA repair · 2024Article
- Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein.Journal of biomolecular structure & dynamics · 2023Article
- Xeroderma Pigmentosum Complementation Group C (XPC): Emerging Roles in Non-Dermatologic Malignancies.Frontiers in oncology · 2022Review
- Pathways of DNA Demethylation.Advances in experimental medicine and biology · 2022Article
- Impact of DNA sequences on DNA 'opening' by the Rad4/XPC nucleotide excision repair complex.DNA repair · 2021Article
- Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation.Nature communications · 2021Article
- Tethering-facilitated DNA 'opening' and complementary roles of β-hairpin motifs in the Rad4/XPC DNA damage sensor protein.Nucleic acids research · 2020Article
- The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage.Nucleic acids research · 2020Review
- PPRC1, but not PGC-1α, levels directly correlate with expression of mitochondrial proteins in human dermal fibroblasts.Genetics and molecular biology · 2020Article
- Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences.Genes & development · 2019Review
- Chromatin Remodeling and Epigenetic Regulation in Plant DNA Damage Repair.International journal of molecular sciences · 2019Review
- Impaired DNA demethylation of C/EBP sites causes premature aging.Genes & development · 2018Article
- Defining the impact of sumoylation on substrate binding and catalysis by thymine DNA glycosylase.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent state during cellular reprogramming requires DNA methylation to silence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcription. The removal of methylated cytosines requires the base excision repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation occurs in a rapid and site-specific manner remains unclear. Here we show that the XPC DNA repair complex is a potent accelerator of global and locus-specific DNA demethylation in somatic and pluripotent stem cells. XPC cooperates with TDG genome-wide to stimulate the turnover of essential intermediates by overcoming slow TDG-abasic product dissociation during active DNA demethylation. We further establish that DNA demethylation induced by XPC expression in somatic cells overcomes an early epigenetic barrier in cellular reprogramming and facilitates the generation of more robust induced pluripotent stem cells, characterized by enhanced pluripotency-associated gene expression and self-renewal capacity. Taken together with our previous studies establishing the XPC complex as a transcriptional coactivator, our findings underscore two distinct but complementary mechanisms by which XPC influences gene regulation by coordinating efficient TDG-mediated DNA demethylation along with active transcription during somatic cell reprogramming.
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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.