LIG4

The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq]

ligase IV, DNA, ATP-dependent

DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:8798671, PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226).
Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226).
Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226).
LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226).
Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069).
Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421).
LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242).

Cell cycleIEA:UniProtKB-KW
Cell divisionIEA:UniProtKB-KW
Cell population proliferationISS:UniProtKB
Cellular response to ionizing radiationManual Assertion Based On ExperimentIGI:UniProtKB
Cellular response to lithium ionIEA:Ensembl
Central nervous system developmentISS:UniProtKB
Chromosome organizationISS:UniProtKB
DNA biosynthetic processIEA:InterPro
DNA ligationManual Assertion Based On ExperimentIDA:UniProtKB
DNA ligation involved in DNA recombinationISS:UniProtKB
DNA ligation involved in DNA repairManual Assertion Based On ExperimentIDA:UniProtKB
DNA replicationIEA:UniProtKB-KW
Double-strand break repairManual Assertion Based On ExperimentIDA:UniProtKB
Double-strand break repair via classical nonhomologous end joiningManual Assertion Based On ExperimentIMP:BHF-UCL
Double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIDA:UniProtKB
Establishment of integrated proviral latencyTAS:Reactome
Immunoglobulin V(D)J recombinationManual Assertion Based On ExperimentIBA:GO_Central
In utero embryonic developmentISS:UniProtKB
Isotype switchingISS:UniProtKB
Negative regulation of neuron apoptotic processISS:UniProtKB
Neuron apoptotic processISS:UniProtKB
Nucleotide-excision repair, DNA gap fillingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of chromosome organizationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of fibroblast proliferationISS:UniProtKB
Positive regulation of neurogenesisISS:UniProtKB
Pro-B cell differentiationISS:UniProtKB
Response to gamma radiationISS:UniProtKB
Response to X-rayManual Assertion Based On ExperimentIMP:UniProtKB
Single strand break repairManual Assertion Based On ExperimentIDA:UniProtKB
Somatic stem cell population maintenanceISS:UniProtKB
T cell differentiation in thymusISS:UniProtKB
T cell receptor V(D)J recombinationISS:UniProtKB
V(D)J recombinationManual Assertion Based On ExperimentIDA:UniProtKB

Nucleus

LIG4 syndrome (LIG4S):
Characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID):
A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.