Evidence map›Paper›PMID 29121353›Full record

ArticleNucleic acids research2017

Secondary structure forming sequences drive SD-MMEJ repair of DNA double-strand breaks.

Varandt Y Khodaverdian, Terrence Hanscom, Amy Marie Yu, Taylor L Yu, Victoria Mak, Alexander J Brown, Steven A Roberts, Mitch McVey

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023
    Review
  8. Article
  9. Review
  10. Tools for Efficient Genome Editing; ZFN, TALEN, and CRISPR.Methods in molecular biology (Clifton, N.J.) · 2022
    Review
  11. Review
  12. Article
  13. Polymerase δ promotes chromosomal rearrangements and imprecise double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Review
  16. Mechanistic basis for microhomology identification and genome scarring by polymerase theta.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  17. Intra-Molecular Homologous Recombination of Scarless Plasmid.International journal of molecular sciences · 2020
    Article
  18. Review
  19. Article
  20. CRISPR Taking the Front Seat in Immunotherapy.Journal of cellular immunology · 2020
    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

8 authors at 2 institutions in 1 country.

Varandt Y KhodaverdianDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Terrence HanscomDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Amy Marie YuDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Taylor L YuDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Victoria MakDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Alexander J BrownSchool of Molecular Biosciences, Washington State University, P100 Dairy Road, Pullman, WA 99164, USA.
Steven A RobertsSchool of Molecular Biosciences, Washington State University, P100 Dairy Road, Pullman, WA 99164, USA.
Mitch McVeyDepartment of Biology, Tufts University, 200 Boston Avenue, Suite 4700, Medford, MA 02155, USA.
Tufts University · USWashington State University · US

Funding

Mutations Arising During DNA RepairP01GM105473 · NIGMS · BRANDEIS UNIVERSITY · PI LOVETT, SUSAN THOMAS · 2014 to 2018
$8.6M
NIGMS NIH HHS P01 GM105473
6 · The paper itself

Abstract

Alternative end-joining (alt-EJ) repair of DNA double-strand breaks is associated with deletions, chromosome translocations, and genome instability. Alt-EJ frequently uses annealing of microhomologous sequences to tether broken ends. When accessible pre-existing microhomologies do not exist, we have postulated that new microhomologies can be created via limited DNA synthesis at secondary-structure forming sequences. This model, called synthesis-dependent microhomology-mediated end joining (SD-MMEJ), predicts that differences between DNA sequences near double-strand breaks should alter repair outcomes in predictable ways. To test this hypothesis, we injected plasmids with sequence variations flanking an I-SceI endonuclease recognition site into I-SceI expressing Drosophila embryos and used Illumina amplicon sequencing to compare repair junctions. As predicted by the model, we found that small changes in sequences near the I-SceI site had major impacts on the spectrum of repair junctions. Bioinformatic analyses suggest that these repair differences arise from transiently forming loops and hairpins within 30 nucleotides of the break. We also obtained evidence for 'trans SD-MMEJ,' involving at least two consecutive rounds of microhomology annealing and synthesis across the break site. These results highlight the importance of sequence context for alt-EJ repair and have important implications for genome editing and genome evolution.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairNucleic Acid ConformationAnimalsAnimals, Genetically ModifiedBase SequenceBinding SitesDeoxyribonucleases, Type II Site-SpecificDNADrosophila melanogasterModels, GeneticPlasmidsSaccharomyces cerevisiae ProteinsDeoxyribonucleases, Type II Site-SpecificDNASaccharomyces cerevisiae ProteinsSCEI protein, S cerevisiae

Identifiers

PMID29121353
PMCPMC5728401
OpenAlexW2767848910

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.