Evidence map›Paper›PMID 28653660›Full record

ArticleNature communications2017

Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.

Susan E Tsutakawa, Mark J Thompson, Andrew S Arvai, Alexander J Neil, Steven J Shaw, Sana I Algasaier, Jane C Kim, L David Finger, Emma Jardine, Victoria J B Gotham and 7 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Nucleic Acids and Electrical Signals.Reviews of physiology, biochemistry and pharmacology · 2025
    Review
  11. Article
  12. Recurrent DNA nicks drive massive expansions of (GAA)Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. A four-point molecular handover during Okazaki maturation.Nature structural & molecular biology · 2023
    Article
  20. Article

8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Susan E TsutakawaMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Mark J ThompsonCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Andrew S ArvaiDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Alexander J NeilDepartment of Biology, Tufts University, Medford, Massachusetts 02155, USA.
Steven J ShawCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Sana I AlgasaierCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Jane C KimDepartment of Biology, Tufts University, Medford, Massachusetts 02155, USA.
L David FingerCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Emma JardineCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Victoria J B GothamCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Altaf H SarkerBiological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.ORCID 0000-0001-6868-8460
Mai Z HerMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Fahad RashidDivision of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
Samir M HamdanDivision of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.ORCID 0000-0001-5192-1852
Sergei M MirkinDepartment of Biology, Tufts University, Medford, Massachusetts 02155, USA.
Jane A GrasbyCentre for Chemical Biology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
John A TainerMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.ORCID 0000-0003-1659-2429
University of Sheffield · GBLawrence Berkeley National Laboratory · USTufts University · USKing Abdullah University of Science and Technology · SAScripps Research Institute · USThe University of Texas MD Anderson Cancer Center · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Training in Education and Critical Research SkillsK12GM074869 · NIGMS · TUFTS UNIVERSITY BOSTON · PI MOORE, CLAIRE L · 2006 to 2017
$8.5M
REPLICATION OF SIMPLE DNA REPEATSR01GM060987 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MIRKIN, SERGEI · 2001 to 2017
$4.9M
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)R01GM105404 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 2012 to 2015
$2.1M
Integrative modeling of PCNA assemblies engaged in genome duplication and repairR01GM110387 · NIGMS · GEORGIA STATE UNIVERSITY · PI IVANOV, IVAYLO NIKOLAEV · 2015 to 2019
$1.7M
Biotechnology and Biological Sciences Research Council BB/M00404X/1NCI NIH HHS P01 CA092584NIGMS NIH HHS R01 GM060987NIGMS NIH HHS R01 GM105404NIGMS NIH HHS R01 GM110387
6 · The paper itself

Abstract

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5'-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5'-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5'polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via 'phosphate steering', basic residues energetically steer an inverted ss 5'-flap through a gateway over FEN1's active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)

Indexed as

Genomic InstabilityAmino Acid SequenceBinding SitesCatalytic DomainDNADNA RepairDNA ReplicationFlap EndonucleasesHumansMutationPhosphatesSequence AlignmentSubstrate SpecificityDNAFlap EndonucleasesPhosphates

Identifiers

PMID28653660
PMCPMC5490271
OpenAlexW2728852806

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.