Evidence map›Paper›PMID 38242128›Full record

ArticleMolecular cell2024

Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications.

Chunyi Hu, Mason T Myers, Xufei Zhou, Zhonggang Hou, Macy L Lozen, Ki Hyun Nam, Yan Zhang, Ailong Ke

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

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4 · The record

Corrections and comments

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; Department of Biological Sciences, Faculty of Science; Department of Biochemistry, Precision Medicine Translational Research Programme (TRP), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Mason T MyersDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Xufei ZhouDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Zhonggang HouDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Macy L LozenDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Ki Hyun NamCollege of General Education, Kookmin University, Seoul 02707, Republic of Korea.
Yan ZhangDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: yzhangbc@med.umich.edu.
Ailong KeDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA. Electronic address: ailong.ke@cornell.edu.

Funding

PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Mechanistic Investigation of RNA-Mediated Gene Regulation and ImmunityR35GM118174 · NIGMS · YALE UNIVERSITY · PI AILONG KE · 2016 to 2026
$7.9M
Generation of DNA memory by bacterial CRISPR-Cas9 systemsR35GM137883 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Yan Zhang · 2020 to 2026
$3.0M
NIGMS NIH HHS R35 GM118174NIGMS NIH HHS R35 GM137883NIGMS NIH HHS T32 GM007544
6 · The paper itself

Abstract

Type I CRISPR-Cas systems utilize the RNA-guided Cascade complex to identify matching DNA targets and the nuclease-helicase Cas3 to degrade them. Among the seven subtypes, type I-C is compact in size and highly active in creating large-sized genome deletions in human cells. Here, we use four cryoelectron microscopy snapshots to define its RNA-guided DNA binding and cleavage mechanisms in high resolution. The non-target DNA strand (NTS) is accommodated by I-C Cascade in a continuous binding groove along the juxtaposed Cas11 subunits. Binding of Cas3 further traps a flexible bulge in NTS, enabling NTS nicking. We identified two anti-CRISPR proteins AcrIC8 and AcrIC9 that strongly inhibit Neisseria lactamica I-C function. Structural analysis showed that AcrIC8 inhibits PAM recognition through allosteric inhibition, whereas AcrIC9 achieves so through direct competition. Both Acrs potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells, providing the first off-switches for type I CRISPR eukaryotic genome engineering.

Indexed as

CRISPR-Associated ProteinsGene EditingCRISPR-Cas SystemsCryoelectron MicroscopyDNAHumansRNACRISPR-Associated ProteinsDNARNAAcranti-CRISPRCas3CascadeCRISPRgene activationgenome editing

Identifiers

PMID38242128
PMCPMC10857747

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Registered trials

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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.