ArticleCell reports2024
HIRA protects telomeres against R-loop-induced instability in ALT cancer cells.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- Histone chaperone HIRA restrains ferroptosis susceptibility through epigenetic control of iron metabolism in prostate cancer.Science China. Life sciences · 2026Article
- Article
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- TPR is required for circRNA, lncRNA and mRNA nuclear export.Non-coding RNA research · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- Chromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication.bioRxiv : the preprint server for biology · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells.eLife · 2025Article
- Oxidative stress at telomeres triggers internal DNA loops, TRF1 dissociation, and TRF2-dependent R-loops.Nucleic acids research · 2025Article
- Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.Medical oncology (Northwood, London, England) · 2025Review
- Identification of modulators of the ALT pathway through a native FISH-based optical screen.Cell reports · 2025Article
- Telomere interactions and structural variants in ALT cells revealed with TelSPRITE.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
Abstract
Inactivating mutations in chromatin modifiers, like the α-thalassemia/mental retardation, X-linked (ATRX)-death domain-associated protein (DAXX) chromatin remodeling/histone H3.3 deposition complex, drive the cancer-specific alternative lengthening of telomeres (ALT) pathway. Prior studies revealed that HIRA, another histone H3.3 chaperone, compensates for ATRX-DAXX loss at telomeres to sustain ALT cancer cell survival. How HIRA rescues telomeres from the consequences of ATRX-DAXX deficiency remains unclear. Here, using an assay for transposase-accessible chromatin using sequencing (ATAC-seq) and cleavage under targets and release using nuclease (CUT&RUN), we establish that HIRA-mediated deposition of new H3.3 maintains telomeric chromatin accessibility to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) in ATRX-DAXX-deficient ALT cells. We show that the HIRA-UBN1/UBN2 complex deposits new H3.3 to prevent TERRA R-loop buildup and transcription-replication conflicts (TRCs) at telomeres. Furthermore, HIRA-mediated H3.3 incorporation into telomeric chromatin links productive ALT to the phosphorylation of serine 31, an H3.3-specific amino acid, by Chk1. Therefore, we identify a critical role for HIRA-mediated H3.3 deposition that ensures the survival of ATRX-DAXX-deficient ALT cancer cells.
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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 Socratic graph.