Evidence map›Paper›PMID 22244820›Full record

ReviewMechanisms of ageing and development2012

Double strand binding-single strand incision mechanism for human flap endonuclease: implications for the superfamily.

Susan E Tsutakawa, John A Tainer

Abstract readReview
In one paragraph

Review in Mechanisms of ageing and development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Influence of a single-nucleotide polymorphism of the DNA mismatch repair-related gene exonuclease-1 (rs9350) with prostate cancer risk among Chinese people.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. 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

2 authors at 2 institutions in 1 country.

Susan E TsutakawaLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
John A Tainer
Lawrence Berkeley National Laboratory · USScripps Research Institute · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
FEN1 STRUCTURES AND HUMAN GENOME STABILITYR01CA081967 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 1999 to 2013
$4.2M
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
NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA081967NCI NIH HHS R01CA081967NIGMS NIH HHS R01 GM105404
6 · The paper itself

Abstract

Detailed structural, mutational, and biochemical analyses of human FEN1/DNA complexes have revealed the mechanism for recognition of 5' flaps formed during lagging strand replication and DNA repair. FEN1 processes 5' flaps through a previously unknown, but structurally elegant double-stranded (ds) recognition/single stranded (ss) incision mechanism that both selects for 5' flaps and selects against ss DNA or RNA, intact dsDNA, and 3' flaps. Two major DNA binding interfaces, including a K(+) bridge between the DNA and the H2TH motif, are spaced one helical turn apart and together select for substrates with dsDNA. A conserved helical gateway and a helical cap protects the two-metal active site and selects for ss flaps with free termini. Structures of substrate and product reveal an unusual step between binding substrate and incision that involves a double base unpairing with incision occurring in the resulting unpaired DNA or RNA. Ordering of the active site requires a disorder-to-order transition induced by binding of an unpaired 3' flap, which ensures that the product is ligatable. Comparison with FEN superfamily members, including XPG, EXO1, and GEN1, identifies superfamily motifs such as the helical gateway that select for ss-dsDNA junctions and provides key biological insights into nuclease specificity and regulation.

Indexed as

DNA RepairDNA ReplicationBinding SitesDNA, Single-StrandedFlap EndonucleasesHumansModels, MolecularNucleic Acid ConformationNucleotide MotifsProtein ConformationSubstrate SpecificityDNA, Single-StrandedFEN1 protein, humanFlap Endonucleases

Identifiers

PMID22244820
PMCPMC3345168
OpenAlexW2072391897

What OpenQuestion holds

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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.