Evidence map›Paper›PMID 39060288›Full record

ArticleNature communications2024

Dual activities of an X-family DNA polymerase regulate CRISPR-induced insertional mutagenesis across species.

Trevor Weiss, Jitesh Kumar, Chuan Chen, Shengsong Guo, Oliver Schlegel, John Lutterman, Kun Ling, Feng Zhang

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

8 authors.

Trevor Weiss *Department of Plant and Microbial Biology, University of Minnesota, Saint Paul, MN, 55108, USA.ORCID 0000-0002-2373-0802
Jitesh Kumar *Department of Plant and Microbial Biology, University of Minnesota, Saint Paul, MN, 55108, USA.ORCID 0000-0003-1606-3420
Chuan ChenDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.ORCID 0000-0002-0694-0867
Shengsong GuoDepartment of Plant and Microbial Biology, University of Minnesota, Saint Paul, MN, 55108, USA.ORCID 0009-0004-6185-1308
Oliver SchlegelDepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, 55455, USA.
John LuttermanDepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, 55455, USA.
Kun LingDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.ORCID 0000-0002-2388-5492
Feng ZhangDepartment of Plant and Microbial Biology, University of Minnesota, Saint Paul, MN, 55108, USA. zhangumn@umn.edu.ORCID 0000-0002-3539-3655

Funding

NSF | BIO | Division of Integrative Organismal Systems (IOS) IOS-2206920
6 · The paper itself

Abstract

The canonical non-homologous end joining (c-NHEJ) repair pathway, generally viewed as stochastic, has recently been shown to produce predictable outcomes in CRISPR-Cas9 mutagenesis. This predictability, mainly in 1-bp insertions and small deletions, has led to the development of in-silico prediction programs for various animal species. However, the predictability of CRISPR-induced mutation profiles across species remained elusive. Comparing CRISPR-Cas9 repair outcomes between human and plant species reveals significant differences in 1-bp insertion profiles. The high predictability observed in human cells links to the template-dependent activity of human Polλ. Yet plant Polλ exhibits dual activities, generating 1-bp insertions through both templated and non-templated manners. Polλ knockout in plants leads to deletion-only mutations, while its overexpression enhances 1-bp insertion rates. Two conserved motifs are identified to modulate plant Polλ's dual activities. These findings unveil the mechanism behind species-specific CRISPR-Cas9-induced insertion profiles and offer strategies for predictable, precise genome editing through c-NHEJ.

Indexed as

CRISPR-Cas SystemsDNA End-Joining RepairMutagenesis, InsertionalArabidopsisDNA Polymerase betaGene EditingHEK293 CellsHumansSpecies SpecificityDNA Polymerase betaDNA polymerase beta2

Identifiers

PMID39060288
PMCPMC11282277

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.