ArticleNature communications2024
H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
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- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting.Signal transduction and targeted therapy · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Review
- The DNA helicase HELQ promotes replication fork reversal in coordination with BRCA2- and FANCD2-mediated repair pathways.Nucleic acids research · 2026Article
- Targeted inhibition of the CREB1-CtIP axis enhances the efficacy of abiraterone combined with radiotherapy in prostate cancer.Cell death & disease · 2026Article
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Deficiencies in the Fanconi anemia or homologous recombination pathway enhance the antitumor effects of the hypoxia-activated prodrug CP-506.Molecular therapy. Oncology · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- TONSL promotes hepatocellular carcinoma progression and radioresistance by orchestrating DNA damage repair and cell cycle dynamics.Discover oncology · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- MDC1 counteracts replication fork reversal and mediates chemosensitivity in BRCA1/2-deficient tumors.Oncogene · 2026Article
- DDX10 RNA Helicase: Structure, Function, and Oncogenic Roles Across Solid and Hematologic Tumors.Genes · 2026Review
- Higher Selective Targeting of Telomeric Multimeric G-quadruplex by Natural Product Berberine.Current medicinal chemistry · 2026Article
- PARP inhibitor maintenance in first-line ovarian cancer therapy: emerging standards and strategies to overcome resistance.American journal of cancer research · 2026Review
- Dual Sensitization Enables Synergistic Photodynamic Therapy and Radiotherapy for Breast Cancer.Research (Washington, D.C.) · 2026Article
- Excessive cholesterol accelerates intervertebral disc degeneration by promoting the polarization of M1 macrophages.Lipids in health and disease · 2025Article
- RAD51 is chromatin enriched and targetable in BRCA1-deficient cells.Molecular cell · 2025Article
- Automated machine learning profiling with MAP-HR for quantifying homologous recombination foci in patient samples.NAR cancer · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair.
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