Evidence map›Paper›PMID 23470991›Full record

ArticleNucleic acids research2013

Harnessing mutagenic homologous recombination for targeted mutagenesis in vivo by TaGTEAM.

Shawn P Finney-Manchester, Narendra Maheshri

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

29 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. A meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Evolution and synthetic biology.Current opinion in microbiology · 2023
    Review
  8. A Rapid Antibody Enhancement Platform inACS synthetic biology · 2023
    Article
  9. Review
  10. Article
  11. In vivo hypermutation and continuous evolution.Nature reviews. Methods primers · 2022
    Article
  12. Article
  13. Review
  14. Review
  15. Automated Continuous Evolution of ProteinsACS synthetic biology · 2020
    Article
  16. Review
  17. Article
  18. Tools and systems for evolutionary engineering of biomolecules and microorganisms.Journal of industrial microbiology & biotechnology · 2019
    Review
  19. Review
  20. Probing pathways of adaptation with continuous evolution.Current opinion in systems biology · 2019
    Article
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

2 authors at 1 institution in 1 country.

Shawn P Finney-ManchesterDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Narendra Maheshri
Massachusetts Institute of Technology · US

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
NIEHS NIH HHS P30 ES002109NIEHS NIH HHS P30-ES002109
6 · The paper itself

Abstract

A major hurdle to evolutionary engineering approaches for multigenic phenotypes is the ability to simultaneously modify multiple genes rapidly and selectively. Here, we describe a method for in vivo-targeted mutagenesis in yeast, targeting glycosylases to embedded arrays for mutagenesis (TaGTEAM). By fusing the yeast 3-methyladenine DNA glycosylase MAG1 to a tetR DNA-binding domain, we are able to elevate mutation rates >800 fold in a specific ∼20-kb region of the genome or on a plasmid that contains an array of tetO sites. A wide spectrum of transitions, transversions and single base deletions are observed. We provide evidence that TaGTEAM generated point mutations occur through error-prone homologous recombination (HR) and depend on resectioning and the error-prone polymerase Pol ζ. We show that HR is error-prone in this context because of DNA damage checkpoint activation and base pair lesions and use this knowledge to shift the primary mutagenic outcome of targeted endonuclease breaks from HR-independent rearrangements to HR-dependent point mutations. The ability to switch repair in this way opens up the possibility of using targeted endonucleases in diverse organisms for in vivo-targeted mutagenesis.

Indexed as

Recombinational DNA RepairDeoxyribonucleases, Type II Site-SpecificDNA GlycosylasesMutagenesis, Site-DirectedMutation RateOperator Regions, GeneticPoint MutationRecombinant Fusion ProteinsRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDeoxyribonucleases, Type II Site-SpecificDNA Glycosylasesendodeoxyribonuclease FokIMAG1 protein, S cerevisiaeRecombinant Fusion ProteinsRepressor ProteinsSaccharomyces cerevisiae Proteinstetracycline resistance-encoding transposon repressor protein

Identifiers

PMID23470991
PMCPMC3643572
OpenAlexW2121795359

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.