Evidence map›Paper›PMID 35835111›Full record

ArticleMolecular cell2022

Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools.

Chunyi Hu, Dongchun Ni, Ki Hyun Nam, Sonali Majumdar, Justin McLean, Henning Stahlberg, Michael P Terns, Ailong Ke

Abstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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

45 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Transcription-Coupled Repair and R-Loop Crosstalk in Genome Stability.International journal of molecular sciences · 2025
    Review
  15. Article
  16. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors.

Chunyi HuDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA.
Dongchun NiLaboratory of Biological Electron Microscopy, Institute of Physics, Faculty of Basic Sciences, Swiss Federal Institute of Technology (EPFL), Cubotron, Route de la Sorge, 1015 Lausanne, Switzerland; Department of Fundamental Biology, Faculty of Biology and Medicine, University of Lausanne (UNIL), 1011 Lausanne, Switzerland.
Ki Hyun NamDepartment of Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
Sonali MajumdarDepartment of Biochemistry and Molecular Biology, Department of Genetics, and Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Justin McLeanDepartment of Biochemistry and Molecular Biology, Department of Genetics, and Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Henning StahlbergLaboratory of Biological Electron Microscopy, Institute of Physics, Faculty of Basic Sciences, Swiss Federal Institute of Technology (EPFL), Cubotron, Route de la Sorge, 1015 Lausanne, Switzerland; Department of Fundamental Biology, Faculty of Biology and Medicine, University of Lausanne (UNIL), 1011 Lausanne, Switzerland.
Michael P TernsDepartment of Biochemistry and Molecular Biology, Department of Genetics, and Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Ailong KeDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA. Electronic address: ailong.ke@cornell.edu.

Funding

Mechanistic Investigation of RNA-Mediated Gene Regulation and ImmunityR35GM118174 · NIGMS · YALE UNIVERSITY · PI AILONG KE · 2016 to 2026
$7.9M
CRISPR Capture, Destroy, and Counter-Attack MechanismsR35GM118160 · NIGMS · UNIVERSITY OF GEORGIA · PI TERNS, MICHAEL P · 2016 to 2025
$5.8M
NIGMS NIH HHS R35 GM118160NIGMS NIH HHS R35 GM118174
6 · The paper itself

Abstract

Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degradation. Contrary to this model, here, we show that type I-A Cascade and Cas3 function as an integral effector complex. We provide four cryoelectron microscopy (cryo-EM) snapshots of the Pyrococcus furiosus (Pfu) type I-A effector complex in different stages of DNA recognition and degradation. The HD nuclease of Cas3 is autoinhibited inside the effector complex. It is only allosterically activated upon full R-loop formation, when the entire targeted region has been validated by the RNA guide. The mechanistic insights inspired us to convert Pfu Cascade-Cas3 into a high-sensitivity, low-background, and temperature-activated nucleic acid detection tool. Moreover, Pfu CRISPR-Cas3 shows robust bi-directional deletion-editing activity in human cells, which could find usage in allele-specific inactivation of disease-causing mutations.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsCryoelectron MicroscopyDNAEndonucleasesGene EditingHumansRNACRISPR-Associated ProteinsDNAEndonucleasesRNACas3CRISPRdeletiongenome editingnucleic acid detectiontype I CRISPR-Cas

Identifiers

PMID35835111
PMCPMC9357151

What OpenQuestion holds

Textmetadata
LicenceTDM
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.