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FLASH GENE
Symbol FEN1 contributors: shn/pgu - updated : 09-09-2015
HGNC name flap structure-specific endonuclease 1
HGNC id 3650
Location 11q12.2      Physical location : 61.560.149 - 61.564.707
Synonym name
  • maturation factor 1
  • DNase IV
  • Synonym symbol(s) FEN1L1, FENL2, MF1, RAD2, FEN-1
    EC.number 3.1.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 4.56 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S1765 - D11S4076 - FEN1 - D11S4205 - D11S1883 - qter
    Physical map
    PGA5 11q13 pepsinogen 5, group I (pepsinogen A) FLJ32009 11q12.3 hypothetical protein FLJ32009 DDB1 11q12-q13.1 damage-specific DNA binding protein 1, 127kDa DKFZP586B1621 11q12.3 DKFZP586B1621 protein MGC20446 11q12.3 hypothetical protein MGC20446 HSPC196 11q12.3 hypothetical protein HSPC196 MGC:13379 11q13.1 HSPC244 FLJ12529 11q12.3 pre-mRNA cleavage factor I, 59 kDa subunit FLJ20487 11q12.3 hypothetical protein FLJ20487 FLJ32771 11q12.3 IIIG9 protein SYT7 11q12-q13.1 synaptotagmin VII LOC390205 11 similar to leucine-rich repeat-containing 10; leucine-rich repeat protein; leucine-rich containing 10 RPLP0P2 11cen-q12 ribosomal protein, large, P0 pseudogene 2 C11orf11 11q13.1 chromosome 11 open reading frame 11 C11orf9 11q12-q13.1 chromosome 11 open reading frame 9 C11orf10 11q12-q13.1 chromosome 11 open reading frame 10 FEN1 11q13.1 flap structure-specific endonuclease 1 FADS1 11q12.2-q13.1 fatty acid desaturase 1 FADS2 11q12-q13.1 fatty acid desaturase 2 FADS3 11q12-q13.1 fatty acid desaturase 3 RAB3IL1 11q12-q13.1 RAB3A interacting protein (rabin3)-like 1 VMD2 11q12-q13.1 vitelliform macular dystrophy (Best disease, bestrophin) FTH1 11q13.1 ferritin, heavy polypeptide 1 LOC387774 11 LOC387774 LOC390206 11 similar to 40S ribosomal protein S2 INCENP 11q12-q13 inner centromere protein antigens 135/155kDa LOC283236 11q12.3 similar to eukaryotic translation elongation factor 1 delta isoform 1; guanine nucleotide exchange protein SCGB1D1 11q13 secretoglobin, family 1D, member 1 SCGB2A1 11q13 secretoglobin, family 2A, member 1 SCGB1D2 11q13 secretoglobin, family 1D, member 2 SCGB2A2 11q13 secretoglobin, family 2A, member 2 ASRGL1 11q12.3 asparaginase like 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2265 42.4 380 - 1995 7774922
    - initiation site - - - localizes to mitochondria 2013 23675412
  • truncated FEN1 isoform with a mitochondrial targeting signal
  • can bind to R-loops, and to a lesser extent to D-loops
  • likely interacts with RNA/DNA hybrids in mitochondrial DNA, such as those found at the origin of replication
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Reproductivefemale systembreastmammary gland  
     female systemuteruscervix highly
    Respiratorylung    
    Urinarybladder   highly
    Visualeye    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • a N terminal flexible loop required for cleavage
  • a catalytic site
  • a DNA-binding motif
  • C-terminal domain implicated in re-initiation of stalled replication forks , and with the nuclease domain of are involved in interaction with TERT, whereas the PCNA binding ability of FEN1 is dispensable for the interaction
  • HOMOLOGY
    interspecies homolog to rad27, Saccharomyces cerevisiae
    ortholog to Fen1, Rattus norvegicus
    ortholog to Fen1, Mus musculus
    Homologene
    FAMILY
  • XPG/RAD2 endonuclease family
  • FEN1 subfamily
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nucleus,nucleolus
    text
  • colocalize in the nucleus with NEIL1
  • localizes to the mammalian telomere
  • RECQL and FEN1 were constitutively present at telomeres and their binding to the telomeric chromatin was enhanced following DNA damage
  • basic FUNCTION
  • essential for cell-free DNA replication
  • involved in long patch base excision repair, DNA replication, where it processes Okazaki fragments, recombination and repair where it interacts with PCNA complex and DNA and acts as an exonuclease
  • playing a role in transcription and elongation
  • has a role in multiple DNA metabolic pathways and critical role in maintaining the integrity of the genome
  • FEN1-WRN complex has an important role in DNA metabolism
  • plays an important role in DNA replication,repair and recombination
  • important for processing DNA ends during homologous recombination
  • plays a vital role in maintaining genome stability
  • can regulate telomerase activity at telomeres in mammalian cells
  • might be required for telomerase-mediated telomere maintenance
  • role in repairing mitochondrial oxidative DNA damage
  • contributing to telomere stability and integrity in cells that rely on the alternative lengthening of telomere mechanism
  • could participate in strand displacement repair synthesis (long patch repair LP-BER) mediated by FEN1 and stimulated by PCNA and strongly implicated in a distinct subpathway of LP-BER in replicating genomes
  • structure-specific endonuclease that plays an important role in DNA metabolism
  • required for replication of lagging strand telomeres
  • maintains stable telomeres by facilitating replication through the G-rich lagging strand telomere, thereby ensuring high fidelity telomere replication
  • promotes efficient re-initiation of stalled replication forks
  • necessary for efficient replication of telomeres, and potentially promotes replication fork re-initiation within telomeric sequences
  • important guardian of genome stability, and major player in telomere maintenance
  • FEN1 and TERT complex could be participating in crucial events at telomeres and understanding the role of this complex can pave way for telomerase based cancer therapeutics
  • FEN1, EXO1, ERCC5, and GEN1 are junction specific enzymes that require three separate binding sites for DNA and that incise one base pair into the duplex region of the substrate
  • cell-cycle-dependent timing of FEN1 nuclease activity is essential for cell-cycle progression and the maintenance of genome stability
  • plays an essential role in keeping genomic instability and preventing tumorigenesis
  • conserved collaboration of RECQL with FEN1, suggesting both overlapping and specialized roles of RECQL in the processing of DNA structure intermediates proposed to arise during replication, repair and recombination
  • canonical lagging strand DNA replication protein, required for normal, complete leading strand replication at telomeres
  • removes flaps containing trinucleotide repeats (TNR) sequences at a rate slower than mixed sequence flaps of the same length
  • CELLULAR PROCESS nucleotide, replication
    nucleotide, repair, base excision repair
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    text maintenance of genomic stability
    PATHWAY
    metabolism
    signaling
    removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis
    a component
  • complexing with PCNA
  • FEN1 forms a complex with telomerase in a cell cycle dependent manner
  • EXO1, ERCC5, and GEN1, whose activities span multiple DNA repair pathways, are members of the 5 prime nuclease superfamily with FEN1
  • INTERACTION
    DNA telomeric DNA
    RNA
    small molecule
    protein
  • (RFC1) complex stimulates the nuclease activity of human FEN1 in an ATP-independent manner
  • PCNA(to promote the coordination of enzymatic activities during DNA replication and repair), but this interaction is dispensable for its role at the telomere
  • WRN stimulating FEN1 cleavage
  • AP endonuclease 1
  • Cyclin dependent kinase 2
  • E1A binding protein p300
  • HNRNPA1
  • RecQ protein like 2 (WRN)
  • RecQ helicase-like (BLM)
  • telomerase (catalytic subunit hTERT)
  • telomere-binding proteins TRF2
  • with FEN1, DNA2 is thought to be involved in the repair of oxidative lesions in DNA molecules
  • co-localizes to stalled replication forks where it interacts with the RecQ helicase, WRN, and is postulated to re-initiate stalled DNA replication forks
  • FEN1 and telomerase association occurs throughout the S phase, with the maximum association in the mid S phase
  • both MUS81-EME1 and MUS81-EME2 increased the activity of FEN1, but FEN1 did not stimulate the activity of MUS81-EME1/EME2
  • FANCA, a protein that recognizes 5' flap structures and is involved in DNA repair and maintenance of replication forks, constantly stimulates FEN1-mediated incision of both DNA and RNA flaps
  • regulation of FEN1 by FANCA contributes to the maintenance of genomic stability
  • cell & other
    REGULATION
    activated by PCNA (prolifering cell nuclear antigen)
    WRN (Werner syndrome protein)
    acetylated by the transcriptional coactivator EP300
    APE1 stimulates FFEN1 and coordinates FEN1 and LIG1 in B long patch BER
    HIV-1 Integrase
    Other FEN1 phosphorylation stimulated its SUMOylation, which in turn stimulated its ubiquitination and ultimately led to its degradation via the proteasome pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    mutated in Cockayne syndrome, severe form
    tumoral     --over  
    in lung cancer
    tumoral somatic mutation      
    abrogated two of three nuclease activities of flap endonuclease 1 in several cancer
    Susceptibility
  • to developing breast cancer
  • to glioma
  • Variant & Polymorphism SNP
  • FEN1-69GG genotypes were significantly correlated to increased risk for developing breast cancer compared with the -69AA genotype
  • FEN1-69GG or 4150GG genotype were significantly associated to increased glioma risk
  • Candidate gene
    Marker
  • is a promising biomarker in breast and ovarian epithelial cancer
  • Therapy target
    ANIMAL & CELL MODELS
  • Fen1 depleted null mice showed embryonic lethality and the blastocysts displayed proliferation failure and increased sensitivity to gamma radiation