Evidence map›Paper›PMID 34486521›Full record

ArticleeLife2021

Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.

Luka Bacic, Guillaume Gaullier, Anton Sabantsev, Laura C Lehmann, Klaus Brackmann, Despoina Dimakou, Mario Halic, Graeme Hewitt, Simon J Boulton, Sebastian Deindl

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Cryo-EM structure of ALC1 in an open conformation bound to a PARylated nucleosome.Acta crystallographica. Section D, Structural biology · 2026
    Article
  3. TFAM organizes DNA into compact higher order structures.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. CHD1L in cancer and beyond: structure, oncogenic functions, and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Beyond the mono-nucleosome.Biochemical Society transactions · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. 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 · 2024
    Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Luka Bacic *Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-6896-3506
Guillaume Gaullier *Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-3405-6021
Anton SabantsevDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-8559-8894
Laura C LehmannDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-2518-5606
Klaus BrackmannDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Despoina DimakouDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-1424-5469
Mario HalicDepartment of Structural Biology, St Jude Children's Research Hospital, Memphis, United States.ORCID 0000-0002-0061-7372
Graeme HewittThe Francis Crick Institute, London, United Kingdom.
Simon J BoultonThe Francis Crick Institute, London, United Kingdom.
Sebastian DeindlDepartment of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.ORCID 0000-0001-6807-8654
Uppsala University · SEThe Francis Crick Institute · GBSt. Jude Children's Research Hospital · US

Funding

Structural and functional studies of chromatin modifiersR01GM135599 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI HALIC, MARIO · 2020 to 2023
$1.5M
Cancer Research UK 28990Cancer Research UK FC0010048Medical Research Council FC0010048NIGMS NIH HHS R01 GM135599Wellcome TrustWellcome Trust FC0010048
6 · The paper itself

Abstract

The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks.

Indexed as

Chromatin Assembly and DisassemblyPoly ADP RibosylationCarrier ProteinsCryoelectron MicroscopyDNA-Binding ProteinsDNA HelicasesHumansKineticsModels, MolecularNuclear ProteinsNucleosomesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesProtein BindingProtein ConformationRecombinant ProteinsCarrier ProteinsCHD1L protein, humanDNA-Binding ProteinsDNA HelicasesHPF1 protein, humanNuclear ProteinsNucleosomesPARP1 protein, humanPARP2 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesRecombinant ProteinsALC1/CHD1Lchromatinchromosomesgene expressionhumanmolecular biophysicsnucleosomePARP1poly(ADP-ribose)ylationremodelingstructural biology

Identifiers

PMID34486521
PMCPMC8463071
OpenAlexW3198206851

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.