ArticleScience advances2020
The chromatin remodeler ALC1 underlies resistance to PARP inhibitor treatment.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Multilevel Mechanisms of Cancer Drug Resistance.International journal of molecular sciences · 2024Pooled it
- Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation.FEBS letters · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Evolving Treatments and Resistance Mechanisms in Prostate Cancer Therapeutics.ACS pharmacology & translational science · 2026Review
- Repression of EGFR by new biguanide 4C potentiated ovarian cancer to PARP inhibitors through down-regulation of BRCA2 and Rad51.Cell death & disease · 2026Article
- Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.Protein & cell · 2026Article
- Chromatin adaptation and histone remodeling as mechanisms of PARP inhibitor resistance and therapeutic vulnerability.Frontiers in pharmacology · 2026Review
- 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
- Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers.DNA repair · 2024Review
- PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells.Cell death & disease · 2024Article
- CHD1L Regulates Cell Survival in Breast Cancer and Its Inhibition by OTI-611 Impedes the DNA Damage Response and Induces PARthanatos.International journal of molecular sciences · 2024Article
- Article
- Nucleolytic processing of abasic sites underlies PARP inhibitor hypersensitivity in ALC1-deficient BRCA mutant cancer cells.Nature communications · 2024Article
- The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity.Nucleic acids research · 2024Article
- Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells.Scientific reports · 2024Article
- Histone ADP-ribosylation promotes resistance to PARP inhibitors by facilitating PARP1 release from DNA lesions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The recruitment of ACF1 and SMARCA5 to DNA lesions relies on ADP-ribosylation dependent chromatin unfolding.Molecular biology of the cell · 2024Article
3 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
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly(ADP-ribose) polymerase (PARP) inhibitors are used in the treatment of BRCA-deficient cancers, with treatments currently extending toward other homologous recombination defective tumors. In a genome-wide CRISPR knockout screen with olaparib, we identify ALC1 (Amplified in Liver Cancer 1)-a cancer-relevant poly(ADP-ribose)-regulated chromatin remodeling enzyme-as a key modulator of sensitivity to PARP inhibitor. We found that ALC1 can remove inactive PARP1 indirectly through binding to PARylated chromatin. Consequently, ALC1 deficiency enhances trapping of inhibited PARP1, which then impairs the binding of both nonhomologous end-joining and homologous recombination repair factors to DNA lesions. We also establish that ALC1 overexpression, a common feature in multiple tumor types, reduces the sensitivity of BRCA-deficient cells to PARP inhibitors. Together, we conclude that ALC1-dependent PARP1 mobilization is a key step underlying PARP inhibitor resistance.
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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.