ArticleNature cell biology2021
ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 144 citations in OpenAlex.
- Endogenous replication stress creates a unique therapeutic window for ALC1 targeting.EMBO reports · 2026Article
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα.Nature communications · 2026Article
- Structural basis of end processing in the nucleosome by polynucleotide kinase phosphatase.bioRxiv : the preprint server for biology · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.Nature communications · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- Nucleosome unwrapping and PARP1 allostery drive affinities for chromatin and DNA breaks.Nature communications · 2025Article
- Targeting CHD1L suppresses prostate cancer progression via the FOXO3-PUMA axis.Journal of translational medicine · 2025Article
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- Base excision repair in chromatin: A tug-of-war for DNA damage.DNA repair · 2025Review
- Chromatin relaxation dynamics and histone PTMs in the early DNA damage response.Cancer biology & medicine · 2025Article
- The Role of Non-Coding Regions in Breast Cancer: From Gene Regulation to Therapeutic Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Review
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of breast cancer gene (BRCA)-mutant cells and enhanced sensitivity to PARPi by up to 250-fold, while overcoming several resistance mechanisms. ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of base damage repair factors. This resulted in an accumulation of replication-associated DNA damage, increased PARP trapping and a reliance on HR. These findings establish PAR-dependent chromatin remodelling as a mechanistically distinct aspect of PARPi responses and therapeutic target in HR-deficient cancers.
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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.