Evidence map›Paper›PMID 32355159›Full record

ArticleNature communications2020

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Beeke Wienert, David N Nguyen, Alexis Guenther, Sharon J Feng, Melissa N Locke, Stacia K Wyman, Jiyung Shin, Katelynn R Kazane, Georgia L Gregory, Matthew A M Carter and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.8field-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

68 citing papers in PubMed, 113 citations in OpenAlex.

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8 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

15 authors at 6 institutions in 2 countries.

Beeke Wienert *Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.ORCID http://orcid.org/0000-0002-9867-0795
David N Nguyen *Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.ORCID http://orcid.org/0000-0001-6808-2717
Alexis GuentherDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA.ORCID http://orcid.org/0000-0002-1231-1557
Sharon J FengInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.
Melissa N LockeDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA.ORCID http://orcid.org/0000-0001-8162-1471
Stacia K WymanInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.ORCID http://orcid.org/0000-0002-8937-8397
Jiyung ShinDepartment of Biology, Institute of Molecular Health Sciences, ETH Zürich, 8093, Zurich, Switzerland.
Katelynn R KazaneInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.
Georgia L GregoryGladstone Institutes, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-4918-9444
Matthew A M CarterGladstone Institutes, San Francisco, CA, 94158, USA.
Francis WrightDepartment of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
Bruce R ConklinGladstone Institutes, San Francisco, CA, 94158, USA.
Alex MarsonInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.ORCID http://orcid.org/0000-0002-2734-5776
Chris D RichardsonInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA. chris.richardson@lifesci.ucsb.edu.ORCID http://orcid.org/0000-0003-3122-4851
Jacob E CornInnovative Genomics Institute, University of California, Berkeley, CA, 94703, USA. jacob.corn@biol.ethz.ch.ORCID http://orcid.org/0000-0002-7798-5309
Gladstone Institutes · USInnovative Genomics Institute · USUniversity of California, San Francisco · USETH Zurich · CHUniversity of California, Santa Barbara · USUniversity of California, Berkeley · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Discovering mechanisms that regulate organelle autophagyDP2HL141006 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI CORN, JACOB ELLERY · 2017 to 2017
$2.4M
NHLBI NIH HHS DP2 HL141006NIAID NIH HHS L40 AI140341NIAID NIH HHS P30 AI027763
6 · The paper itself

Abstract

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.

Indexed as

CRISPR-Cas SystemsRecombinational DNA RepairCell Cycle ProteinsDNA Breaks, Double-StrandedGene EditingGenetic EngineeringHCT116 CellsHEK293 CellsHeLa CellsHomologous RecombinationHumansK562 CellsPhenotypeProtein Serine-Threonine KinasesRNA, Guide, CRISPR-Cas SystemsS PhaseCDC7 protein, humanCell Cycle ProteinsProtein Serine-Threonine KinasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID32355159
PMCPMC7193628
OpenAlexW3021554387

What OpenQuestion holds

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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.