ArticleMolecular and cellular biology2004
Saccharomyces cerevisiae flap endonuclease 1 uses flap equilibration to maintain triplet repeat stability.
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.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- The New Face of Dynamic Mutation-The CAA [CAG]n CAA CAG Motif as a Mutable Unit in theInternational journal of molecular sciences · 2024Article
- Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.Nucleic acids research · 2023Article
- Article
- Review
- Error-prone, stress-induced 3' flap-based Okazaki fragment maturation supports cell survival.Science (New York, N.Y.) · 2021Article
- Restarted replication forks are error-prone and cause CAG repeat expansions and contractions.PLoS genetics · 2021Article
- FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.Journal of Huntington's disease · 2021Review
- Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.Trends in genetics : TIG · 2018Review
- Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.Nucleic acids research · 2018Article
- Replication stalling and DNA microsatellite instability.Biophysical chemistry · 2017Review
- Myotonic dystrophy: disease repeat range, penetrance, age of onset, and relationship between repeat size and phenotypes.Current opinion in genetics & development · 2017Review
- Requirement for flap endonuclease 1 (FEN1) to maintain genomic stability and transcriptional gene silencing in Arabidopsis.The Plant journal : for cell and molecular biology · 2016Article
- AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism during base excision repair.Nucleic acids research · 2015Article
- Expansion of CAG repeats in Escherichia coli is controlled by single-strand DNA exonucleases of both polarities.Genetics · 2014Article
- Base excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion.Nucleic acids research · 2014Article
- A saccharomyces cerevisiae RNase H2 interaction network functions to suppress genome instability.Molecular and cellular biology · 2014Article
- A Whole Genome Screen for Minisatellite Stability Genes in Stationary-Phase Yeast Cells.G3 (Bethesda, Md.) · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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.
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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.