Evidence map›Paper›PMID 15082797›Full record

ArticleMolecular and cellular biology2004

Saccharomyces cerevisiae flap endonuclease 1 uses flap equilibration to maintain triplet repeat stability.

Yuan Liu, Haihua Zhang, Janaki Veeraraghavan, Robert A Bambara, Catherine H Freudenreich

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

44 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
  2. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
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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 2 institutions in 1 country.

Yuan LiuDepartment of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642,USA.
Haihua Zhang
Janaki Veeraraghavan
Robert A Bambara
Catherine H Freudenreich
University of Rochester · USTufts University · US

Funding

ENZYMATIC MECHANISMS OF DNA SYNTHESISR01GM024441 · NIGMS · UNIVERSITY OF ROCHESTER · PI BAMBARA, ROBERT A · 1985 to 2011
$3.8M
Stability &Fragility of Trinucleotide Repeats in YeastR01GM063066 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI FREUDENREICH, CATHERINE H · 2001 to 2010
$2.4M
NIGMS NIH HHS GM24441NIGMS NIH HHS GM63066NIGMS NIH HHS R01 GM024441NIGMS NIH HHS R01 GM063066
6 · The paper itself

Abstract

Flap endonuclease 1 (FEN1) is a central component of Okazaki fragment maturation in eukaryotes. Genetic analysis of Saccharomyces cerevisiae FEN1 (RAD27) also reveals its important role in preventing trinucleotide repeat (TNR) expansion. In humans such expansion is associated with neurodegenerative diseases. In vitro, FEN1 can inhibit TNR expansion by employing its endonuclease activity to compete with DNA ligase I. Here we employed two yeast FEN1 nuclease mutants, rad27-G67S and rad27-G240D, to further define the mechanism by which FEN1 prevents TNR expansion. Using a yeast artificial chromosome system that can detect both TNR instability and fragility, we demonstrate that the G240D but not the G67S mutation increases both the expansion and fragility of a CTG tract in vivo. In vitro, the G240D nuclease is proficient in cleaving a fixed nonrepeat double flap; however, it exhibits severely impaired cleavage of both nonrepeat and CTG-containing equilibrating flaps. In contrast, wild-type FEN1 and the G67S mutant exhibit more efficient cleavage on an equilibrating flap than on a fixed CTG flap. The degree of TNR expansion and the amount of chromosome fragility observed in the mutant strains correlate with the severity of defective flap cleavage in vitro. We present a model to explain how flap equilibration and the unique tracking mechanism of FEN1 can collaborate to remove TNR flaps and prevent repeat expansion.

Indexed as

Chromosomal InstabilityTrinucleotide RepeatsBase SequenceDNADNA DamageDNA RepairDNA ReplicationFlap EndonucleasesHumansMolecular Sequence DataMutationNucleic Acid ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNAFlap EndonucleasesOkazaki fragmentsSaccharomyces cerevisiae Proteins

Identifiers

PMID15082797
PMCPMC387768
OpenAlexW2094502358

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.