ArticleMolecular cell2021
Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 160 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα.Nature communications · 2026Article
- 8oxoG:A Is Structurally Accommodated in the Nucleosome Core Particle, Yet Inaccessible to MUTYH-Initiated DNA Repair.Biomolecules · 2026Article
- Distinct ATRX functions cooperate with 9-1-1 and CST complexes to safeguard replication and telomere integrity.Nature structural & molecular biology · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.Protein & cell · 2026Article
- Article
- RPA exhaustion activates SLFN11 to eliminate cells with heightened replication stress.Nature cell biology · 2026Article
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation.Cell reports · 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
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer.Cancer science · 2025Article
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- Histone PARylation factor 1: a review of its role in the DNA damage response.Nucleic acids research · 2025Review
- EXO1 as a therapeutic target for Fanconi Anaemia, ZRSR2 and BRCA1-A complex deficient cancers.Nature communications · 2025Article
- Disrupted transcriptional networks regulated by CHD1L during neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant.Nucleic acids research · 2025Article
- Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 3 countries.
Funding
Abstract
Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD 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.