LIG4

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Ligase IV, DNA, ATP-dependent
Protein LIG4 PDB 1ik9.png
PDB rendering based on 1ik9.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbol LIG4
External IDs OMIM601837 MGI1335098 HomoloGene1736 GeneCards: LIG4 Gene
EC number 6.5.1.1
RNA expression pattern
PBB GE LIG4 206235 at tn.png
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.[1]

Function[edit]

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[edit]

LIG4 has been shown to interact with XRCC4 via its BRCT domain.[2][3] This interaction stabilizes LIG4 protein in cells; cells that are deficient for XRCC4, such as XR-1 cells, have reduced levels of LIG4.[4]

Mechanism[edit]

LIG4 is an ATP-dependent DNA ligase. LIG4 uses ATP to adenylate itself and then transfers the AMP group to the 5' phosphate of one DNA end. Nucleophilic attack by the 3' hydroxyl group of a second DNA end and release of AMP yield the ligation product. Adenylation of LIG4 is stimulated by XRCC4 and XLF.[5]

References[edit]

  1. ^ "Entrez Gene: LIG4 ligase IV, DNA, ATP-dependent". 
  2. ^ Deshpande RA, Wilson TE (October 2007). "Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4". DNA Repair (Amst.) 6 (10): 1507–16. doi:10.1016/j.dnarep.2007.04.014. PMC 2064958. PMID 17567543. 
  3. ^ Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L (December 2001). "Crystal structure of an Xrcc4-DNA ligase IV complex". Nat. Struct. Biol. 8 (12): 1015–9. doi:10.1038/nsb725. PMID 11702069. 
  4. ^ Bryans M, Valenzano MC, Stamato TD (January 1999). "Absence of DNA ligase IV protein in XR-1 cells: evidence for stabilization by XRCC4". Mutat. Res. 433 (1): 53–8. doi:10.1016/s0921-8777(98)00063-9. PMID 10047779. 
  5. ^ Mahaney BL, Hammel M, Meek K, Tainer JA, Lees-Miller SP (February 2013). "XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair". Biochem. Cell Biol. 91 (1): 31–41. doi:10.1139/bcb-2012-0058. PMID 23442139. 

Further reading[edit]