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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
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