LIG4

From Wikipedia, the free encyclopedia

Ligase IV, DNA, ATP-dependent

PDB rendering based on 1ik9.

Available structures: 1ik9, 2e2w

Identifiers

Symbol(s)

LIG4;

External IDs

OMIM: 601837 MGI: 1335098 HomoloGene: 1736

Gene ontology
Molecular Function:	• nucleotide binding • DNA binding • DNA ligase (ATP) activity • protein binding • ATP binding • ligase activity
Cellular Component:	• intracellular • nucleus
Biological Process:	• single strand break repair • DNA replication • DNA recombination • cell cycle • cell division

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_002312 (mRNA)
NP_002303 (protein)

NM_176953 (mRNA)
NP_795927 (protein)

Location

Chr 13: 107.66 - 107.67 Mb

Chr 8: 9.97 - 9.98 Mb

Pubmed search

[1]

[2]

LIG4 is a human gene that encodes the protein DNA Ligase IV.^[1]

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.

[edit] References

^ Entrez Gene: LIG4 ligase IV, DNA, ATP-dependent.

[edit] 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. PMID 7760816.
Robins P, Lindahl T (1996). "DNA ligase IV from HeLa cell nuclei.". J. Biol. Chem. 271 (39): 24257–61. 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. 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. 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. 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. 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. 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. 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. 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. PMID 12023982.
Mahajan KN, Nick McElhinny SA, Mitchell BS, Ramsden DA (2002). "Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair.". Mol. Cell. Biol. 22 (14): 5194–202. PMID 12077346.
Roth DB (2002). "Amplifying mechanisms of lymphomagenesis.". Mol. Cell 10 (1): 1–2. 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. 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. 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. PMID 12477932.