LIG4

Ligase IV, DNA, ATP-dependent
PDB rendering based on 1ik9.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1IK9, 2E2W, 3II6, 3VNN, 3W1B, 3W1G, 3W5O, 4HTO, 4HTP
Identifiers
Symbol	LIG4
External IDs	OMIM: 601837 MGI: 1335098 HomoloGene: 1736 GeneCards: LIG4 Gene
EC number	6.5.1.1
Gene Ontology Molecular function • DNA binding • DNA ligase activity • DNA ligase (ATP) activity • protein binding • ATP binding • protein C-terminus binding • ligase activity • metal ion binding Cellular component • condensed chromosome • nucleus • nucleoplasm • nucleolus • cytoplasm • plasma membrane • focal adhesion • DNA-dependent protein kinase-DNA ligase 4 complex • DNA ligase IV complex • nonhomologous end joining complex Biological process • single strand break repair • in utero embryonic development • pro-B cell differentiation • DNA ligation • lagging strand elongation • DNA repair • nucleotide-excision repair, DNA gap filling • double-strand break repair • double-strand break repair via nonhomologous end joining • cell cycle • central nervous system development • cell proliferation • response to X-ray • response to gamma radiation • viral reproduction • viral reproductive process • T cell differentiation in thymus • V(D)J recombination • immunoglobulin V(D)J recombination • T cell receptor V(D)J recombination • somatic stem cell maintenance • negative regulation of neuron apoptotic process • isotype switching • positive regulation of fibroblast proliferation • positive regulation of neurogenesis • DNA ligation involved in DNA recombination • DNA ligation involved in DNA repair • chromosome organization • cell division • neuron apoptotic process • cellular response to lithium ion • establishment of integrated proviral latency Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3981	319583
Ensembl	ENSG00000174405	ENSMUSG00000049717
UniProt	P49917	Q8BTF7
RefSeq (mRNA)	NM_001098268	NM_176953
RefSeq (protein)	NP_001091738	NP_795927
Location (UCSC)	Chr 13: 108.86 – 108.87 Mb	Chr 8: 9.97 – 9.98 Mb
PubMed search	[1]	[2]

LIG4 is a human gene that encodes the protein DNA Ligase IV.

The protein encoded by this gene is an ATP-dependent DNA ligase that joins double-strand breaks during the non-homologous end joining pathway of double-strand break repair. It is also essential for V(D)J recombination. Lig4 forms a complex with XRCC4, and further interacts with the DNA-dependent protein kinase (DNA-PK) and XLF/Cernunnos, which are also required for NHEJ. The crystal structure of the Lig4/XRCC4 complex has been resolved.^{[citation needed]} Defects in this gene are the cause of LIG4 syndrome. The yeast homolog of Lig4 is Dnl4.

Interactions

LIG4 has been shown to interact with XRCC4.

Further reading

• Wei YF, Robins P, Carter K, et al. (1995). "Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination". Mol. Cell. Biol. 15 (6): 3206–16. PMC 230553. PMID 7760816. 
• Robins P, Lindahl T (1996). "DNA ligase IV from HeLa cell nuclei". J. Biol. Chem. 271 (39): 24257–61. doi:10.1074/jbc.271.39.24257. PMID 8798671. 
• Grawunder U, Wilm M, Wu X, et al. (1997). "Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells". Nature 388 (6641): 492–5. doi:10.1038/41358. PMID 9242410. 
• Critchlow SE, Bowater RP, Jackson SP (1997). "Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV". Curr. Biol. 7 (8): 588–98. doi:10.1016/S0960-9822(06)00258-2. PMID 9259561. 
• Grawunder U, Zimmer D, Leiber MR (1998). "DNA ligase IV binds to XRCC4 via a motif located between rather than within its BRCT domains". Curr. Biol. 8 (15): 873–6. doi:10.1016/S0960-9822(07)00349-1. PMID 9705934. 
• Grawunder U, Zimmer D, Fugmann S, et al. (1998). "DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes". Mol. Cell 2 (4): 477–84. doi:10.1016/S1097-2765(00)80147-1. PMID 9809069. 
• Riballo E, Critchlow SE, Teo SH, et al. (1999). "Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient". Curr. Biol. 9 (13): 699–702. doi:10.1016/S0960-9822(99)80311-X. PMID 10395545. 
• Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806. 
• Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA (2000). "Ku Recruits the XRCC4-Ligase IV Complex to DNA Ends". Mol. Cell. Biol. 20 (9): 2996–3003. doi:10.1128/MCB.20.9.2996-3003.2000. PMC 85565. PMID 10757784. 
• Chen L, Trujillo K, Sung P, Tomkinson AE (2000). "Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase". J. Biol. Chem. 275 (34): 26196–205. doi:10.1074/jbc.M000491200. PMID 10854421. 
• Lee KJ, Huang J, Takeda Y, Dynan WS (2000). "DNA ligase IV and XRCC4 form a stable mixed tetramer that functions synergistically with other repair factors in a cell-free end-joining system". J. Biol. Chem. 275 (44): 34787–96. doi:10.1074/jbc.M004011200. PMID 10945980. 
• Riballo E, Doherty AJ, Dai Y, et al. (2001). "Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity". J. Biol. Chem. 276 (33): 31124–32. doi:10.1074/jbc.M103866200. PMID 11349135. 
• Sibanda BL, Critchlow SE, Begun J, et al. (2002). "Crystal structure of an Xrcc4-DNA ligase IV complex". Nat. Struct. Biol. 8 (12): 1015–9. doi:10.1038/nsb725. PMID 11702069. 
• O'Driscoll M, Cerosaletti KM, Girard PM, et al. (2002). "DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency". Mol. Cell 8 (6): 1175–85. doi:10.1016/S1097-2765(01)00408-7. PMID 11779494. 
• Kuschel B, Auranen A, McBride S, et al. (2002). "Variants in DNA double-strand break repair genes and breast cancer susceptibility". Hum. Mol. Genet. 11 (12): 1399–407. doi:10.1093/hmg/11.12.1399. PMID 12023982. 
• Mahajan KN, Nick McElhinny SA, Mitchell BS, Ramsden DA (2002). "Association of DNA Polymerase μ (pol μ) with Ku and Ligase IV: Role for pol μ in End-Joining Double-Strand Break Repair". Mol. Cell. Biol. 22 (14): 5194–202. doi:10.1128/MCB.22.14.5194-5202.2002. PMC 139779. PMID 12077346. 
• Roth DB (2002). "Amplifying mechanisms of lymphomagenesis". Mol. Cell 10 (1): 1–2. doi:10.1016/S1097-2765(02)00573-7. PMID 12150897. 
• Smogorzewska A, Karlseder J, Holtgreve-Grez H, et al. (2003). "DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2". Curr. Biol. 12 (19): 1635–44. doi:10.1016/S0960-9822(02)01179-X. PMID 12361565. 
• Roddam PL, Rollinson S, O'Driscoll M, et al. (2003). "Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination". J. Med. Genet. 39 (12): 900–5. doi:10.1136/jmg.39.12.900. PMC 1757220. PMID 12471202. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.