Evidence map›Paper›PMID 22918592›Full record

ReviewSub-cellular biochemistry2012

The wonders of flap endonucleases: structure, function, mechanism and regulation.

L David Finger, John M Atack, Susan Tsutakawa, Scott Classen, John Tainer, Jane Grasby, Binghui Shen

Open access · greenAbstract readReview
In one paragraph

Review in Sub-cellular biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
25.6field-weighted citation impact, top 1% 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

33 citing papers in PubMed, 55 citations in OpenAlex.

  1. DNA polymerase I: structure, activity, and function in bacterial DNA replication and repair.Critical reviews in biochemistry and molecular biology · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Base Excision DNA Repair in Plants:International journal of molecular sciences · 2023
    Review
  7. Article
  8. Article
  9. XPG: a multitasking genome caretaker.Cellular and molecular life sciences : CMLS · 2022
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review
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

7 authors at 4 institutions in 3 countries.

L David FingerDepartment of Chemistry, Centre for Chemical Biology, Krebs Institute, University of Sheffield, Sheffield, S3 7HF, UK, d.finger@sheffield.ac.uk.
John M Atack
Susan Tsutakawa
Scott Classen
John Tainer
Jane Grasby
Binghui Shen
University of Sheffield · GBScripps Research Institute · USLawrence Berkeley National Laboratory · USZhejiang University · CN

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Function Analysis of FEN-1 Nuclease in Genome StabilityR01CA073764 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI BINGHUI SHEN · 2002 to 2026
$7.9M
FEN1 STRUCTURES AND HUMAN GENOME STABILITYR01CA081967 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 1999 to 2013
$4.2M
Biotechnology and Biological Sciences Research Council BBF0147321NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA073764NCI NIH HHS R01CA073764NCI NIH HHS R01 CA081967
6 · The paper itself

Abstract

Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase α are displaced by DNA polymerase δ to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication.

Indexed as

AnimalsDNADNA LigasesDNA Polymerase IIIDNA ReplicationFlap EndonucleasesHumansProliferating Cell Nuclear AntigenStructure-Activity RelationshipDNADNA LigasesDNA Polymerase IIIFEN1 protein, humanFlap EndonucleasesOkazaki fragmentsProliferating Cell Nuclear Antigen

Identifiers

PMID22918592
PMCPMC3728657
OpenAlexW1508748054

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.