ArticleCancer research2018
Role of Chromatin Damage and Chromatin Trapping of FACT in Mediating the Anticancer Cytotoxicity of DNA-Binding Small-Molecule Drugs.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
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- Determining Preclinical Safety of Aclarubicin in Pediatric Malignancies.Pediatric blood & cancer · 2026Article
- Quantitative single-cell imaging suggests increased global chromatin accessibility in tumor versus non-tumor cell lines.iScience · 2025Article
- Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.bioRxiv : the preprint server for biology · 2025Article
- The isoflavone genistein selectively stimulates major satellite repeat transcription in mouse heterochromatin.Epigenetics & chromatin · 2025Article
- Article
- CBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.Oncogene · 2025Article
- Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases.Cancers · 2024Article
- Aclarubicin Reduces the Nuclear Mobility of Human DNA Topoisomerase IIβ.International journal of molecular sciences · 2024Article
- Chromatin as an old and new anticancer target.Trends in cancer · 2024Review
- Chromatin damage generated by DNA intercalators leads to degradation of RNA Polymerase II.Nucleic acids research · 2024Article
- The Bisdioxopiperazine ICRF-193 Attenuates LPS-induced IL-1β Secretion by Macrophages.Inflammation · 2024Article
- Comparison of cell response to chromatin and DNA damage.Nucleic acids research · 2023Article
- Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.European journal of medical research · 2023Review
- Aclarubicin stimulates RNA polymerase II elongation at closely spaced divergent promoters.Science advances · 2023Article
- Aclarubicin stimulates RNA polymerase II elongation at closely spaced divergent promoters.bioRxiv : the preprint server for biology · 2023Article
- CBL0137 impairs homologous recombination repair and sensitizes high-grade serous ovarian carcinoma to PARP inhibitors.Journal of experimental & clinical cancer research : CR · 2022Article
- FACT maintains nucleosomes during transcription and stem cell viability in adult mice.EMBO reports · 2022Article
- Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.Medical sciences (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Precisely how DNA-targeting chemotherapeutic drugs trigger cancer cell death remains unclear, as it is difficult to separate direct DNA damage from other effects in cells. Recent work on curaxins, a class of small-molecule drugs with broad anticancer activity, shows that they interfere with histone-DNA interactions and destabilize nucleosomes without causing detectable DNA damage. Chromatin damage caused by curaxins is sensed by the histone chaperone FACT, which binds unfolded nucleosomes becoming trapped in chromatin. In this study, we investigated whether classical DNA-targeting chemotherapeutic drugs also similarly disturbed chromatin to cause chromatin trapping of FACT (c-trapping). Drugs that directly bound DNA induced both chromatin damage and c-trapping. However, chromatin damage occurred irrespective of direct DNA damage and was dependent on how a drug bound DNA, specifically, in the way it bound chromatinized DNA in cells. FACT was sensitive to a plethora of nucleosome perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Strikingly, we found that the cytotoxicity of DNA-binding small molecules correlated with their ability to cause chromatin damage, not DNA damage. Our results suggest implications for the development of chromatin-damaging agents as selective anticancer drugs.
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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.