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FLASH GENE
Symbol TOP1 contributors: mct - updated : 30-11-2015
HGNC name topoisomerase (DNA) I
HGNC id 11986
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an unstructured N-terminal domain of 200 amino acids, poorly conserved N-terminal domain
  • a coiled-coil linker domain of variable length
  • a structured functional domain of 565 AAS that binds and relaxes supercoiled DNA
  • the highly conserved core and C-terminal domains involved in catalysis
    • conjugated Other
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to rattus Top1 (97.3 pc)
    homolog to murine Top1 (97.3 pc)
    Homologene
    FAMILY
  • eukaryotic type I topoisomerase family
    • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • perikaryon
  • very high levels of topoisomerase 1 (TOP1) in the nucleus, and specifically the nucleolus, of human Purkinje neurons (Gorodetsky 2007)
    • basic FUNCTION
  • DNA topoisomerase I, relaxing negatively supercoiled DNA and releasing torsion stress created by DNA transcription
  • catalyzing the ATP independent breakage and rejoining of single strand of DNA
  • involved in DNA repair
  • aborting in cells treated by antitumor drugs with the production of topoisomerase-DNA damage, finally distroyed by ubiquitin after conjugation with SUMO1 (UBL1)
  • function of TOP1 in regulating senescence
  • involvement of TOP1, TDP1 , and single-strand break repair (SSBR) in modulating transcription-dependent CAG repeat contractions
  • is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals
  • initiates an independent form of repair to remove ribonucleotides from genomic DNA
  • TOP1, TOP2A are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
  • controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission
  • during processes such as DNA replication and transcription, DNA topoisomerase I (TOP1) catalyzes the relaxation of DNA supercoils
  • complex interplay between replication and transcription in regulating TOP1-dependent genetic instability
    • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, replication
    nucleotide, recombination
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to single stand
    RNA
    small molecule
    protein
  • CCR7 was found to interact directly with TOPI
  • TOP2A, TOP1 are involved in initiating aphidicolin-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
  • RECQL5 helicase promotes TOP1 SUMOylation by facilitating the interaction between PIAS1, SRSF1 and TOP1
    • cell & other
    REGULATION
    activated by phosphorylation (stimulates its DNA relaxation activity)
    inhibited by camptothecin (specifically)
    Other sumoylation playing a role in partitioning TOP1 between nucleoli and nucleoplasm (Lys-117 being the main site of sumoylation)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with NUP98 in t(11;20)(p15;q11) in therapy related myelodysplastic syndrome
    tumoral   amplification    
    is associated with advanced tumours and poor prognosis in melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS