ArticleNucleic acids research2024
DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Distinct ATRX functions cooperate with 9-1-1 and CST complexes to safeguard replication and telomere integrity.Nature structural & molecular biology · 2026Article
- Review
- SFPQ directs histone H3.3 deposition to R-loops in DNA repeats to protect genome stability.Nature communications · 2026Article
- Daxx-Dependent H3.3 Deposition Promotes Double-Strand Breaks Repair by Homologous Recombination.Cells · 2026Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- LANA-dependent transcription-replication conflicts and R-loops at the terminal repeats (TR) correlate with KSHV episome maintenance.PLoS pathogens · 2025Article
- The Dynamic Regulation of Daxx-Mediated Transcriptional Inhibition by SUMO and PML NBs.International journal of molecular sciences · 2025Review
- Daxx and HIRA go viral - How chromatin remodeling complexes affect DNA virus infection.Tumour virus research · 2025Review
- Clinical Relevance of ATRX/DAXX Gene Mutations and ALT in Functioning Pancreatic Neuroendocrine Tumors.Endocrine pathology · 2025Review
- Multifunctional histone variants in genome function.Nature reviews. Genetics · 2025Review
- Loss of DAXX/ATRX Protein Expression Results in Ischemia Resistance and Radiation Sensitivity in Pancreatic Neuroendocrine Tumor Cells and Is Associated with Improved Response to Trans-Arterial Radioembolization.Neuroendocrinology · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations.
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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.