ArticleNucleic acids research1997
Functional analysis of point mutations in human flap endonuclease-1 active site.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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.
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.
Who cites it
44 citing papers in PubMed, 108 citations in OpenAlex.
- Targeting FEN1 disrupts EIF4A3-mediated MUC1-C autoregulation: a novel strategy to suppress lung adenocarcinoma progression.Cell death & disease · 2026Article
- DNA large fragment deleting by compact, sequence-motif-free and specific TaqTth-hpRNA assisted with the microhomology-mediated end joining pathway.Nucleic acids research · 2025Article
- PARP1-driven repair of topoisomerase IIIα DNA-protein crosslinks by FEN1.Cell reports · 2024Article
- TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.Genome biology · 2024Article
- Modeling DNA trapping of anticancer therapeutic targets using missense mutations identifies dominant synthetic lethal interactions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- R-loops promote trinucleotide repeat deletion through DNA base excision repair enzymatic activities.The Journal of biological chemistry · 2020Article
- Mkt1 is required for RNAi-mediated silencing and establishment of heterochromatin in fission yeast.Nucleic acids research · 2020Article
- Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage.The Journal of biological chemistry · 2018Article
- Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.Cell reports · 2018Article
- Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.Nature communications · 2017Article
- A novel POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine.Familial cancer · 2015Article
- Structural studies of DNA end detection and resection in homologous recombination.Cold Spring Harbor perspectives in biology · 2014Review
- CtIP maintains stability at common fragile sites and inverted repeats by end resection-independent endonuclease activity.Molecular cell · 2014Article
- Rad52/Rad59-dependent recombination as a means to rectify faulty Okazaki fragment processing.The Journal of biological chemistry · 2014Article
- Trypanosome MKT1 and the RNA-binding protein ZC3H11: interactions and potential roles in post-transcriptional regulatory networks.Nucleic acids research · 2014Article
- DNA repair pathways in trypanosomatids: from DNA repair to drug resistance.Microbiology and molecular biology reviews : MMBR · 2014Review
- Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin.Nucleic acids research · 2014Article
- The structure of Escherichia coli ExoIX--implications for DNA binding and catalysis in flap endonucleases.Nucleic acids research · 2013Article
- Flap endonuclease 1.Annual review of biochemistry · 2013Review
- A general approach to break the concentration barrier in single-molecule imaging.Nature methods · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human flap endonuclease-1 (hFEN-1) is highly homologous to human XPG, Saccharomyces cerevisiae RAD2 and S.cerevisiae RTH1 and shares structural and functional similarity with viral exonucleases such as T4 RNase H, T5 exonuclease and prokaryotic DNA polymerase 5'nucleases. Sequence alignment of 18 structure-specific nucleases revealed two conserved nuclease domains with seven conserved carboxyl residues and one positively charged residue. In a previous report, we showed that removal of the side chain of each individual acidic residue results in complete loss of flap endonuclease activity. Here we report a detailed analysis of substrate cleavage and binding of these mutant enzymes as well as of an additional site-directed mutation of a conserved acidic residue (E160). We found that the active mutant (R103A) has substrate binding and cleavage activity indistinguishable from the wild type enzyme. Of the inactive mutants, one (D181A) has substrate binding properties comparable to the wild type, while three others (D34A, D86A and E160A) bind with lower apparent affinity (2-, 9- and 18-fold reduced, respectively). The other mutants (D158A, D179A and D233A) have no detectable binding activity. We interpret the structural implications of these findings using the crystal structures of related enzymes with the flap endonuclease activity and propose that there are two metal ions (Mg2+or Mn2+) in hFEN enzyme. These two metal coordinated active sites are distinguishable but interrelated. One metal site is directly involved in nucleophile attack to the substrate phosphodiester bonds while the other may stabilize the structure for the DNA substrate binding. These two sites may be relatively close since some of carboxyl residues can serve as ligands for both sites.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.