Evidence map›Paper›PMID 40394064›Full record

ArticleNature communications2025

Elucidating the genetic mechanisms governing cytosine base editing outcomes through CRISPRi screens.

Sifeng Gu, Zsolt Bodai, Rachel A Anderson, Hei Yu Annika So, Quinn T Cowan, Alexis C Komor

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. HAMMER: Hairpin-based APOBEC3A-mediated mRNA editing reporter.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
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

6 authors.

Sifeng Gu *Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA.
Zsolt Bodai *Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA.
Rachel A AndersonDepartment of Chemistry and Biochemistry, University of California, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-9497-4134
Hei Yu Annika SoDepartment of Chemistry and Biochemistry, University of California, San Diego, CA, USA.ORCID http://orcid.org/0009-0002-2111-0084
Quinn T CowanDepartment of Chemistry and Biochemistry, University of California, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-8697-8178
Alexis C KomorDepartment of Chemistry and Biochemistry, University of California, San Diego, CA, USA. akomor@ucsd.edu.ORCID http://orcid.org/0000-0001-5043-0998

Funding

MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Chemistry-Biology Interfaces at UCSDT32GM146648 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael D. Burkart, Alexis C. Komor · 2022 to 2026
$876k
National Science Foundation (NSF) MCB-2048207NIGMS NIH HHS T32 GM008326NIGMS NIH HHS T32 GM146648Research Corporation for Science Advancement (Research Corporation) 27975U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM008326U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM146648
6 · The paper itself

Abstract

Cytosine base editors enable programmable and efficient genome editing using an intermediate featuring a U•G mismatch across from a DNA nick. This intermediate facilitates two major outcomes, C•G to T•A and C•G to G•C point mutations, and it is not currently well-understood which DNA repair factors are involved. Here, we couple reporters for cytosine base editing activity with knockdown of 2015 DNA processing genes to identify genes involved in these two outcomes. Our data suggest that mismatch repair factors facilitate C•G to T•A outcomes, while C•G to G•C outcomes are mediated by RFWD3, an E3 ubiquitin ligase. We also propose that XPF, a 3'-flap endonuclease, and LIG3, a DNA ligase, are involved in repairing the intermediate back to the original C•G base pair. Our results demonstrate that competition and collaboration among different DNA repair pathways shape cytosine base editing outcomes.

Indexed as

CRISPR-Cas SystemsCytosineGene EditingDNA Mismatch RepairDNA RepairHEK293 CellsHumansUbiquitin-Protein LigasesCytosineUbiquitin-Protein Ligases

Identifiers

PMID40394064
PMCPMC12092667

What OpenQuestion holds

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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.