Evidence map›Paper›PMID 33848455›Full record

ArticleMolecular cell2021

Impact of chromatin context on Cas9-induced DNA double-strand break repair pathway balance.

Ruben Schep, Eva K Brinkman, Christ Leemans, Xabier Vergara, Robin H van der Weide, Ben Morris, Tom van Schaik, Stefano G Manzo, Daniel Peric-Hupkes, Jeroen van den Berg and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 1 pooled it
13.2field-weighted citation impact, top 1% 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

133 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Article
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  7. Article
  8. Article
  9. Review
  10. Review
  11. In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. CRISPR Interference to Inhibit Oncogenes for Cancer Therapy.International journal of molecular sciences · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Ruben SchepOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Eva K BrinkmanOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Christ LeemansOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Xabier VergaraOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Cell Biology, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Robin H van der WeideOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Ben MorrisDivision of Molecular Carcinogenesis, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Robotics Screening Center, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Tom van SchaikOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Stefano G ManzoOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Daniel Peric-HupkesOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Jeroen van den BergOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Cell Biology, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Roderick L BeijersbergenDivision of Molecular Carcinogenesis, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Robotics Screening Center, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
René H MedemaOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Cell Biology, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands.
Bas van SteenselOncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Department of Cell Biology, Erasmus University Medical Centre, 3015 CN, Rotterdam, the Netherlands. Electronic address: b.v.steensel@nki.nl.
The Netherlands Cancer Institute · NL

Funding

Mapping Technology DevelopmentU54DK107965 · NIDDK · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BELMONT, ANDREW STEVEN · 2015 to 2019
$8.6M
NIDDK NIH HHS U54 DK107965
6 · The paper itself

Abstract

DNA double-strand break (DSB) repair is mediated by multiple pathways. It is thought that the local chromatin context affects the pathway choice, but the underlying principles are poorly understood. Using a multiplexed reporter assay in combination with Cas9 cutting, we systematically measure the relative activities of three DSB repair pathways as a function of chromatin context in >1,000 genomic locations. This reveals that non-homologous end-joining (NHEJ) is broadly biased toward euchromatin, while the contribution of microhomology-mediated end-joining (MMEJ) is higher in specific heterochromatin contexts. In H3K27me3-marked heterochromatin, inhibition of the H3K27 methyltransferase EZH2 reverts the balance toward NHEJ. Single-stranded template repair (SSTR), often used for precise CRISPR editing, competes with MMEJ and is moderately linked to chromatin context. These results provide insight into the impact of chromatin on DSB repair pathway balance and guidance for the design of Cas9-mediated genome editing experiments.

Indexed as

DNA Breaks, Double-StrandedDNA RepairBase SequenceChromatinCRISPR-Associated Protein 9DNA End-Joining RepairEuchromatinGene RearrangementGenome, HumanHeterochromatinHumansINDEL MutationK562 CellsKineticsProtein BindingReproducibility of ResultsChromatinCRISPR-Associated Protein 9EuchromatinHeterochromatinChromatinCRISPRDNA repairdouble strand breakheterochromatinMMEJNHEJnuclear laminareporter assaySSTR

Identifiers

PMID33848455
PMCPMC8153251
OpenAlexW3155689026

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.