Evidence map›Paper›PMID 25500724›Full record

ArticleNature communications2014

Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer.

Qi Zhao, Xiaoyu Xue, Simonne Longerich, Patrick Sung, Yong Xiong

Open access · bronzeAbstract read
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

27 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Qi ZhaoDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Xiaoyu XueDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Simonne LongerichDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Patrick SungDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Yong XiongDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Yale University · US

Funding

Yale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8M
Life Science and Biomedical technology Research center at NSLS-II LSBRP41GM111244 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI MCSWEENEY, SEAN · 2014 to 2018
$16.4M
Mechanistic Dissection of the Fanconi Anemia Pathway of DNA Damage Response and RR01CA168635 · NCI · YALE UNIVERSITY · PI Gary M Kupfer, Patrick Sung · 2013 to 2026
$5.8M
Roles of the RecQ Helicases BLM and RECQ5 in Genome MaintenanceR01ES015632 · NIEHS · YALE UNIVERSITY · PI SUNG, PATRICK · 2007 to 2017
$3.9M
Molecular Basis of BRCA2-mediated DNA Repair and Cancer AvoidanceR01ES015252 · NIEHS · YALE UNIVERSITY · PI SUNG, PATRICK · 2007 to 2016
$3.8M
NCATS NIH HHS UL1 TR000142NCI NIH HHS R01 CA168635NIEHS NIH HHS R01 ES015252NIEHS NIH HHS R01 ES015632NIGMS NIH HHS P41 GM111244
6 · The paper itself

Abstract

Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5' flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA and unwind a 5' flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.

Indexed as

DNA RepairCrystallography, X-RayDNADNA DamageEndodeoxyribonucleasesEscherichia coliExodeoxyribonucleasesGene ExpressionHumansModels, MolecularMultifunctional EnzymesMutationNucleic Acid ConformationProtein BindingProtein MultimerizationProtein Structure, SecondaryDNAEndodeoxyribonucleasesExodeoxyribonucleasesFAN1 protein, humanMultifunctional EnzymesRecombinant Proteins

Identifiers

PMID25500724
PMCPMC4268874
OpenAlexW2029012529

What OpenQuestion holds

Textmetadata
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.