Evidence map›Paper›PMID 29979968›Full record

ArticleMolecular cell2018

Enhanced Bacterial Immunity and Mammalian Genome Editing via RNA-Polymerase-Mediated Dislodging of Cas9 from Double-Strand DNA Breaks.

Ryan Clarke, Robert Heler, Matthew S MacDougall, Nan Cher Yeo, Alejandro Chavez, Maureen Regan, Leslyn Hanakahi, George M Church, Luciano A Marraffini, Bradley J Merrill

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

86 citing papers in PubMed, 156 citations in OpenAlex.

  1. Article
  2. Enhanced editing ofApplied and environmental microbiology · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Engineered transcription-associated Cas9 targeting in eukaryotic cells.bioRxiv : the preprint server for biology · 2024
    Article
  20. Article

26 more citing papers are in PubMed but not listed here.

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 1 country.

Ryan ClarkeDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
Robert HelerLaboratory of Bacteriology, The Rockefeller University, New York, NY 10065, USA.
Matthew S MacDougallDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
Nan Cher YeoDepartment of Genetics, Harvard Medical School, Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Alejandro ChavezDepartment of Genetics, Harvard Medical School, Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Maureen ReganDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA; Genome Editing Core, University of Illinois at Chicago, Chicago, IL 60607, USA.
Leslyn HanakahiDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Rockford Health Science Campus, Rockford, IL 61107, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Luciano A MarraffiniLaboratory of Bacteriology, The Rockefeller University, New York, NY 10065, USA.
Bradley J MerrillDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA; Genome Editing Core, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: merrillb@uic.edu.
University of Illinois Chicago · USHarvard University · USRockefeller University · US

Funding

Strengthening Stakeholder Engagement in Human Research Protections.UL1TR002003 · NCATS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARNIK, NIRANJAN SUBHASH, MERMELSTEIN, ROBIN J. · 2016 to 2024
$33.7M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Using CRISPR immunity to prevent the spread of virulence traits among pathogensDP2AI104556 · NIAID · ROCKEFELLER UNIVERSITY · PI MARRAFFINI, LUCIANO A · 2012 to 2012
$2.5M
Wnt/Beta-catenin and Tcf/Lef factor regulation of pluripotencyR01HD081534 · NICHD · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MERRILL, BRADLEY J · 2014 to 2018
$1.6M
Elucidating the genetic determinants for exit out of pluripotency with a CRISPR-Cas9 genome-wide knockout screenF30HD090938 · NICHD · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MACDOUGALL, MATTHEW STEVEN · 2017 to 2020
$192k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR002003NHGRI NIH HHS RM1 HG008525NIAID NIH HHS DP2 AI104556NICHD NIH HHS F30 HD090938NICHD NIH HHS R01 HD081534
6 · The paper itself

Abstract

The ability to target the Cas9 nuclease to DNA sequences via Watson-Crick base pairing with a single guide RNA (sgRNA) has provided a dynamic tool for genome editing and an essential component of adaptive immune systems in bacteria. After generating a double-stranded break (DSB), Cas9 remains stably bound to DNA. Here, we show persistent Cas9 binding blocks access to the DSB by repair enzymes, reducing genome editing efficiency. Cas9 can be dislodged by translocating RNA polymerases, but only if the polymerase approaches from one direction toward the Cas9-DSB complex. By exploiting these RNA-polymerase/Cas9 interactions, Cas9 can be conditionally converted into a multi-turnover nuclease, mediating increased mutagenesis frequencies in mammalian cells and enhancing bacterial immunity to bacteriophages. These consequences of a stable Cas9-DSB complex provide insights into the evolution of protospacer adjacent motif (PAM) sequences and a simple method of improving selection of highly active sgRNAs for genome editing.

Indexed as

CRISPR-Associated Protein 9DNA Breaks, Double-StrandedDNA RepairGene EditingAnimalsBacteriaBacteriophagesCell LineMiceMouse Embryonic Stem CellsCRISPR-Associated Protein 9Cas9CRISPRDNA repairgenome editingphage biologyRNA polymerasestrand biastranscription

Identifiers

PMID29979968
PMCPMC6063522
OpenAlexW2797604131

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.