ArticleNature communications2021
Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Cryo-EM structure of ALC1 in an open conformation bound to a PARylated nucleosome.Acta crystallographica. Section D, Structural biology · 2026Article
- 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
- Regulation of DNA translocation of chromatin remodeler enzyme Chd1 by exit DNA unwrapping.Life metabolism · 2025Article
- CHD1L in cancer and beyond: structure, oncogenic functions, and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Review
- VRK1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma mediated by SNAI1 via phosphorylating CHD1L.Cell death & disease · 2025Article
- Beyond the mono-nucleosome.Biochemical Society transactions · 2025Review
- Pharmacological mechanism of natural antidepressants: the role of epigenetic modifications.Frontiers in pharmacology · 2025Review
- A review on the relationship between the distal 1q21.1 microdeletion and schizophrenia.Frontiers in genetics · 2025Review
- CHD1L Inhibitor OTI-611 Synergizes with Chemotherapy to Enhance Antitumor Efficacy and Prolong Survival in Colorectal Cancer Mouse Models.International journal of molecular sciences · 2024Article
- The histone demethylase JMJ27 acts during the UV-induced modulation of H3K9me2 landscape and facilitates photodamage repair.Nature plants · 2024Article
- How does CHD4 slide nucleosomes?Biochemical Society transactions · 2024Review
- 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
- PARP-ish: Gaps in Molecular Understanding and Clinical Trials Targeting PARP Exacerbate Racial Disparities in Prostate Cancer.Cancer research · 2024Review
- Energy-driven genome regulation by ATP-dependent chromatin remodellers.Nature reviews. Molecular cell biology · 2024Review
- Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.Nature communications · 2024Article
- Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.Nature communications · 2024Article
- SRSF1 is essential for primary follicle development by regulating granulosa cell survival via mRNA alternative splicing.Cellular and molecular life sciences : CMLS · 2023Article
- Review
- The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families.Nature communications · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer.
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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.