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FLASH GENE
Symbol TONSL contributors: mct/npt - updated : 08-04-2019
HGNC name tonsoku like, DNA repair protein
HGNC id 7801
Corresponding disease
SPODYS Sponastrime dysplasia
Location 8q24.3      Physical location : -
Synonym name
  • I-kappa-B related
  • NF-kappa-B inhibitor-like protein 2
  • nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 2
  • Synonym symbol(s) IKBR, FLJ40087, NFKBIL2
    DNA
    TYPE functioning gene
    STRUCTURE 15.71 kb     26 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    26 - 4519 - 1378 - 2007 17353931
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunetonsils   highly
    Reproductivemale systemprostate  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three ankyrin repeats in the C terminal region (exons 10-12)
  • HOMOLOGY
    interspecies ortholog to Drosophila cactus
    Homologene
    FAMILY
  • not homolog to IKB family
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies
    basic FUNCTION
  • inhibitory cytoplasmic retention protein for NFKB transcription factors
  • importance of TONSL function in replication-fork stability during normal S phase
  • MMS22L-TONSL are components of the replication stress control pathway and provides a resource for discovery of additional components of this pathway
  • MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks
  • MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks
  • cellular functions of TONSL are essential for cellular viability and that hypomorphic variants in TONSL have a deleterious impact at multiple stages of embryonic and postnatal development, particularly during skeletal development
  • is involved in homologous recombination
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • MMS22L-TONSL complex
  • MMS22L-TONSL heterodimer localizes to replication forks under unperturbed conditions and its recruitment is increased during replication stress in human cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NKKB2 (p49) in the IKK complex
  • MMS22L and TONSL interact with each other and with FACT (facilitator of chromatin transcription) and MCM (minichromosome maintenance) complexes
  • physically and functionally interacts with MMS22L that co-purifies with histones, several chromatin remodelling and DNA replication/repair factors
  • in conjunction with its obligate binding partner, MMS22L, is necessary for the repair of replication-associated DNA damage
  • by specifically regulating RAD51 activity at uncoupled replication forks, MMS22L-TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their HR-mediated restart
  • replication-dependent histone chaperones are required for the recruitment of MMS22L-TONSL during homologous recombination (HR) to load RAD51 onto ssDNA
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SPODYS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    of MMS22L or TONSL causes a high level of double-strand breaks (DSBs) during DNA replication; proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors (
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting MMS22L as well as its interaction with TONSL could be a promising strategy for novel cancer treatments, and also improve the efficacy of DNA damaging anticancer drugs
    ANIMAL & CELL MODELS