Gene Ontology annotation through association of InterPro records with GO terms
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InterPro2GO maps for FEN1 domains yield generic terms (catalytic activity, nuclease activity, hydrolase activity on ester bonds) that are correct but uninformative compared to the specific nuclease activities.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
Combined Automated Annotation using Multiple IEA Methods
Identification of zebrafish insertional mutants with defects in visual system development and function.
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The fen1 insertional mutant shows severe retinal defects with smaller eyes, reduced and disorganized retinal neurons, and a thinner optic nerve at 5 dpf.
"Forty loci whose disruption resulted in defects in eye development and/or visual function were identified"
Flap endonuclease 1.
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Comprehensive review of FEN1 as a structure-specific endonuclease central to DNA replication (Okazaki fragment maturation) and repair (long-patch BER, telomere maintenance, stalled fork rescue).
"First discovered as a structure-specific endonuclease that evolved to cut at the base of single-stranded flaps, flap endonuclease (FEN1) is now recognized as a central component of cellular DNA metabolism"
Flap endonuclease 1: a central component of DNA metabolism.
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FEN1 is essential for DNA replication and repair with roles in Okazaki fragment processing and long-patch base excision repair.
"in long-patch base excision repair, a damaged nucleotide is displaced into a flap and removed by FEN1"
Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair.
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FEN1 super-accumulates in the nucleolus for rDNA maintenance and relocalizes to nucleoplasm upon DNA damage via phosphorylation.
"FEN1 is superaccumulated in the nucleolus and plays a role in the resolution of stalled DNA replication forks formed at the sites of natural replication fork barriers"
Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity.
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FEN1/Rad27 localizes to mitochondria in both yeast and mammals, playing a significant role in mtDNA replication and repair.
"Rad27p/FEN1 is localized in the mitochondrial compartment of both yeast and mice and that Rad27p has a significant role in maintaining mtDNA integrity"
Three metal ions participate in the reaction catalyzed by T5 flap endonuclease.
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FEN-catalyzed reactions require at least two divalent metal ions for phosphodiester hydrolysis, with a third ion binding after substrate engagement.
"the T5FEN-catalyzed reaction requires at least three magnesium ions, implying that an additional metal ion is bound"
Proliferation failure and gamma radiation sensitivity of Fen1 null mutant mice at the blastocyst stage.
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Fen1 knockout in mice causes embryonic lethality at the blastocyst stage with S phase arrest, demonstrating essentiality for DNA replication.
"complete depletion of FEN1 causes early embryonic lethality"
Identification of 315 genes essential for early zebrafish development.
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fen1 was identified as one of 315 genes essential for early zebrafish development through retroviral insertional mutagenesis.
"We completed a large insertional mutagenesis screen in zebrafish to identify genes essential for embryonic and early larval development"
Hematopoietic gene expression profile in zebrafish kidney marrow.
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Source of fen1 mRNA sequence from zebrafish kidney marrow.
"We have sequenced 26,143 ESTs and isolated 304 cDNAs with putative full-length ORF from a zebrafish kidney marrow cDNA library"
Falcon deep research report on fen1 (Danio rerio)
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FEN1 is a structure-specific nuclease that recognizes 5'-flap and nicked DNA structures
and hydrolyzes phosphodiester bonds using a two-metal (Mg2+) catalytic center, with at
least three distinguishable nuclease activities (flap endonuclease, 5' exonuclease, gap
endonuclease) primarily acting in lagging-strand replication and repair synthesis.
"three biochemically distinguishable nuclease activities described in the literature: **flap endonuclease (FEN)**, **5′ exonuclease (EXO)**, and **gap endonuclease (GEN)**"
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During Okazaki fragment maturation FEN1 is coordinated on chromatin by PCNA in a toolbelt
mechanism; 2024 cryo-EM of endogenous PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes captured
multiple primer-removal states, with PCNA stimulating FEN1 activity roughly 10-50 fold.
"cryo-EM structural resolution of endogenous **PCNA–FEN1** and **PCNA–FEN1–RNaseH2** complexes, capturing multiple primer-removal states"
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FEN1 also functions in long-patch base excision repair as the core 5'-flap nuclease and,
in recent work, is recruited to DNA-protein crosslinks via PARP1/PARG-dependent
ADP-ribosylation and forms XPA-FEN1-DNA ternary complexes implicating roles beyond
canonical BER/replication.
"describes FEN1 recruitment to DNA–protein crosslinks (DPCs) as regulated by **PARP1/PARG-dependent ADP-ribosylation**"
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Direct zebrafish loss-of-function genetics for fen1 were not retrieved; the strongest
zebrafish-specific evidence is transcript-level induction of fen1 among base excision
repair genes under oxidative/DNA-damaging chemical stress in larvae.
"providing zebrafish-specific assay details including a **fen1 primer** (forward sequence shown in the paper), **amplicon length (138 bp)**, and **PCR efficiency (100%)**"
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FEN1's flap-structure recognition has been engineered into a structure-guided endonuclease
(SGN) fused to FokI that cleaves reporter and endogenous loci in zebrafish embryos,
demonstrating translational use of FEN1 biochemistry in this vertebrate model.
"engineered a **structure-guided endonuclease (SGN)** composed of **FEN-1** (structure recognition of a flap) fused to the FokI cleavage domain, and demonstrated cleavage of reporter and endogenous loci in **zebrafish embryos**"