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FLASH GENE
Symbol NHEJ1 contributors: mct/npt - updated : 11-07-2015
HGNC name nonhomologous end-joining factor 1
HGNC id 25737
Corresponding disease
NBSLD2 Nijmegen breakage syndrome -like disorder 2
PMG1 polymicrogyria
TBCIM T and B Cell Combined Immunodeficiency with Microcephaly
Location 2q35      Physical location : 219.940.050 - 220.025.587
Synonym name
  • cernunnos
  • XRCC4-like factor
  • Synonym symbol(s) XLF, FLJ12610, XRCC4L
    DNA
    TYPE functioning gene
    STRUCTURE 85.54 kb     8 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2119 33.2 299 - 2006 16439204
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     intestinesmall intestine  highly
     liver   moderately
    Nervousbrain   highly
    Reproductivefemale systemuteruscervix highly
     male systemtestis  moderately
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • stretches of particularly high sequence conservation in its N-terminal region
  • a globular head domain followed by a coiled-coil or stalk terminating in an unstructured C-terminal region (CTR), but the stalk region folds back upon itself
  • a putative nuclear localization sequence at its very C terminus (KRKK)
  • HOMOLOGY
    interspecies homolog to murine Nhej1 (74.9 pc)
    intraspecies homolog to XRCC4
    Homologene
    FAMILY
  • XLF family
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • constituting a novel core component of the mammalian DNA nonhomologous end-joining apparatus, might be involved in nonhomologous end-joining pathway of DNA double-strand break repair
  • acting as a novel DNA repair factor
  • plays a role in the development of the central nervous system
  • required for cellular survival in response to DNA double-strand break-generating agents
  • promotes the preservation of 3prime overhangs, restricts nucleotide loss and thereby promotes accuracy of DSB joining by XRCC4-DNA Ligase IV during NHEJ and V(D)J recombination
  • required for double-strand break (DSB) repair and V(D)J recombination
  • may serve as a bridge between XRCC4 and the other NHEJ factors located at DNA ends
  • may participate in reconfiguration of the end bound NHEJ factors to allow XRCC4 access to the DNA termini
  • acting in concert with XRCC6/XRCC5 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are noncomplementary or partially complementary
  • role in repair of DSBs and maintenance of genomic stability under replication stress conditions
  • core protein of the nonhomologous end-joining pathway of DNA double-strand break repair
  • essential for gap filling by either polymerase during nonhomologous end joining, suggesting that it plays a major role in aligning the two DNA ends in the repair complex
  • XRCC4 and NHEJ1 filaments are suitable to align DNA molecules and function to facilitate LigIV end joining required for DSB repair
  • NHEJ1, ATM and H2AFX all have fundamental roles in processing and joining DNA ends during V(D)J recombination, but these roles have been masked by unanticipated functional redundancies
  • involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair
  • influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis
  • in addition to end joining, TP53BP1 and NHEJ1 have overlapping functions in tumor suppression
  • DNA repair factor of the nonhomologous end-joining machinery
  • implicated in DSB pathway choice regulation, and is a non-essential, but critical, C-NHEJ-repair factor
  • XRCC4 and NHEJ1 are two structurally related proteins that function in DNA double-strand break (DSB) repair
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, repair
    PHYSIOLOGICAL PROCESS development
    text
  • B and T cells differentiation
  • central nervous system development
  • PATHWAY
    metabolism
    signaling
    a component
  • key constituent of the DNA end-joining reaction
  • could be a third partner in the XRCC4/LIG4 complex
  • INTERACTION
    DNA binding in a length-dependent manner
    RNA
    small molecule
    protein
  • interacting with XRCC4 and XRCC4-Ligase IV complex
  • interaction between NHEJ1 and XRCC4 is mediated via head-to-head interactions and in the XLF·XRCC4·BRCT complex, alternating repeating units of XLF and XRCC4·BRCT place the BRCT domain on one side of the filament
  • XRCC4 and NHEJ1 interactions promotes alignment of long DNA substrates to facilitate ligation
  • PRKDC has fundamental roles in Classical nonhomologous end joining (C-NHEJ) processes beyond end processing that have been masked by functional overlaps with NHEJ1
  • XRCC4 interacts with NHEJ1, and XRCC4 and NHEJ1 form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair
  • is thought to stimulate the LIG4 activity toward incompatible or mismatched DNA ends
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) TBCIM , PMG1 , NBSLD2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   translocation    
    interrupted in a patient with polymicrogyria in a translocation t(2;7)(q35;p22)
    tumoral somatic mutation      
    missense Cernunnos mutation in a diffuse large B cell lymphoma
    constitutional       loss of function
    reduces thymocyte life span and alters the T cell repertoire
    constitutional       loss of function
    leads to premature aging of hematopoietic stem cells (HSCs), measured by decreased functional capacity in transplantation assays, preferential myeloid reconstitution, and reduced self-renewal at a young age
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Xlf-deficient mice have relatively normal lymphocyte development and their lymphocytes support normal V(D)J recombination
  • Xlf-deficient murine lymphocytes show no measurable defects in V(D)J recombination
  • 53bp1-/-Xlf-/- mice are born alive and develop thymic lymphomas with translocations involving the T-cell receptor loci