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FLASH GENE
Symbol LIG3 contributors: mct/npt - updated : 01-10-2015
HGNC name ligase III, DNA, ATP-dependent
HGNC id 6600
Location 17q12      Physical location : 33.307.516 - 33.332.088
Synonym name
  • polydeoxyribonucleotide synthase [ATP]
  • ligase II, DNA, ATP-dependent
  • DNA ligase III
    • Synonym symbol(s) LIG2
    EC.number 6.5.1.1
    DNA
    TYPE functioning gene
    STRUCTURE 24.57 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 3103 102 949 found in the nucleus and the mitochondria 2013 2401308
  • variant (beta)
  • germ line-specific splicing isoform
    • 20 - 3722 108.7 1009 ubiquitous, found in the nucleus and the mitochondria 2013 2401308
  • variant (alpha)
  • functional redundancy between DNA ligase III alpha and DNA ligase I in excision repair
  • essential for DNA replication in the absence of the replicative DNA ligase, DNA ligase I
  • is a component of an alternative non-homologous end joining (NHEJ) pathway for DNA double-strand break (DSB) repair
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuteruscervix highly
     male systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a BRCT domain
  • a PARP-type zinc finger
    • HOMOLOGY
    Homologene
    FAMILY
  • DNA ligase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • present in the mitochondria, where its role in mitochondrial DNA (mtDNA) maintenance is independent of XRCC1
    • basic FUNCTION
  • can correct defective DNA strand-break repair
    • and sister chromatid exchange following treatment with ionizing radiation and alkylating agents
  • required for microhomology-mediated end joining of DNA double-strand breaks
  • critical biological role of LIG3 is to maintain mtDNA integrity and not XRCC1-dependent DNA repair
  • LIG3 function was central to mitochondrial DNA maintenance 0)
  • promotes alternative nonhomologous end-joining during chromosomal translocation formation
  • crucial for cell survival due to its catalytic function in mitochondria
  • restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR)
  • XRCC1, a LIG3-stabilizing cofactor, and LIG3 itself have been very widely assumed to provide major end-ligation functions in A-EJ (alternative end-joining)
  • remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria
  • LIG1 and LIG3 cooperate in alternative non-homologous end-joining
  • LIG1 is not absolutely required for cellular DNA replication and repair and either LIG3 or LIG4 can substitute for the role of LIG1 in joining Okazaki fragments
  • LIG3 isoforms were seven times more efficient than LIG1 at ligating nicked DNA under optimal conditions
    • CELLULAR PROCESS nucleotide, replication
    nucleotide, repair, recombination
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with XRCC1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with DNA-repair protein XRCC1 (translocation of XRCC1 with LIG3 from centrosomes to chromosomes in response to DNA damage in mitotic cells)
  • LIG1 was critical for DNA repair, but acted in a cooperative manner with LIG3
  • interacting with POLG (interaction of DNA ligase III and DNA polymerase gamma is required for proper maintenance of the mitochondrial genome)
  • functional flexibility and interchangeability between LIG1 and LIG3
  • DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS