Evidence map›Paper›PMID 27133026›Full record

ArticleStructure (London, England : 1993)2016

Indirect DNA Sequence Recognition and Its Impact on Nuclease Cleavage Activity.

Abigail R Lambert, Jazmine P Hallinan, Betty W Shen, Jennifer K Chik, Jill M Bolduc, Nadia Kulshina, Lori I Robins, Brett K Kaiser, Jordan Jarjour, Kyle Havens and 2 more

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Advances in CRISPR/Cas-Based Strategies on Zoonosis.Transboundary and emerging diseases · 2023
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Applications of Alternative Nucleases in the Age of CRISPR/Cas9.International journal of molecular sciences · 2017
    Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Abigail R LambertDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Jazmine P HallinanDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Betty W ShenDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Jennifer K ChikDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Jill M BolducDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Nadia KulshinaDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA.
Lori I RobinsPhysical Sciences Division, School of STEM, University of Washington, 18115 Campus Way Northeast, Bothell, WA 98011, USA.
Brett K KaiserDepartment of Biology, Seattle University, 901 12th Avenue, Seattle, WA 98122, USA.
Jordan Jarjourbluebird bio Inc. Suite 207, 1616 Eastlake Avenue East, Seattle, WA 98102, USA.
Kyle Havensbluebird bio Inc. Suite 207, 1616 Eastlake Avenue East, Seattle, WA 98102, USA.
Andrew M ScharenbergSeattle Children's Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA.
Barry L StoddardDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025, Seattle, WA 98109, USA. Electronic address: bstoddar@fredhutch.org.

Funding

MegaTALS: hyperspecific reagents for targeted gene modification and correctionR01GM105691 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 2014 to 2022
$2.7M
Directed Protein Evolution for Design of LAGLIDADGs with Novel Recognition SpeciRL1CA133832 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI SCHARENBERG, ANDREW M. · 2007 to 2011
$2.2M
Zinc-dependent regulation of gene expressionR01GM105695 · NIGMS · OHIO STATE UNIVERSITY · PI BIRD, AMANDA JANE · 2014 to 2018
$1.4M
NCI NIH HHS RL1 CA133832NIGMS NIH HHS R01 GM105691NIGMS NIH HHS R01 GM105695
6 · The paper itself

Abstract

LAGLIDADG meganucleases are DNA cleaving enzymes used for genome engineering. While their cleavage specificity can be altered using several protein engineering and selection strategies, their overall targetability is limited by highly specific indirect recognition of the central four base pairs within their recognition sites. In order to examine the physical basis of indirect sequence recognition and to expand the number of such nucleases available for genome engineering, we have determined the target sites, DNA-bound structures, and central four cleavage fidelities of nine related enzymes. Subsequent crystallographic analyses of a meganuclease bound to two noncleavable target sites, each containing a single inactivating base pair substitution at its center, indicates that a localized slip of the mutated base pair causes a small change in the DNA backbone conformation that results in a loss of metal occupancy at one binding site, eliminating cleavage activity.

Indexed as

Base SequenceBinding SitesDeoxyribonucleasesDNADNA CleavageModels, MolecularNucleic Acid ConformationProtein ConformationSubstrate SpecificityDeoxyribonucleasesDNA

Identifiers

PMID27133026
PMCPMC4899242

What OpenQuestion holds

Textmetadata
LicenceTDM
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.