InterPro domain: IPR044125

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP ( 6.5.1.1 ), the other NAD ( 6.5.1.2 ), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [ 1 , 2 ].

This entry represents the adenylation domain found in DNA ligase 4.

There are three classes of ATP-dependent DNA ligase in eukaryotic cells (I, III and IV). DNA ligase IV is required for DNA non-homologous end joining pathways, including recombination of the V(D)J immunoglobulin gene segments in cells of the mammalian immune system. DNA ligases have a highly modular architecture consisting of a unique arrangement of two or more discrete domains. The adenylation and C-terminal oligonucleotide/oligosaccharide binding (OB)-fold domains comprise a catalytic core unit that is common to all members of the ATP-dependent DNA ligase family. The adenylation domain binds ATP and contains many of the active-site residues [ 3 , 4 ].

DNA ligase 4 is involved in DNA double-strand break repair [ 5 ]. In higher eukaryotes it forms a complex with XRCC4, which is responsible for the ligation step during the DNA-PK-dependent non-homologous end joining (D-NHEJ) [ 6 , 7 ]. The Ku component of the DNA-PK (DNA-dependent protein kinase) complex contributes to the recruitment of the LIG4-XRCC4 complex at the DNA break site [ 8 ].

1. Location of the active site for enzyme-adenylate formation in DNA ligases. Proc. Natl. Acad. Sci. U.S.A. 88, 400-4
2. Mammalian DNA ligases. Annu. Rev. Biochem. 61, 251-81
3. Eukaryotic DNA ligases: structural and functional insights. Annu. Rev. Biochem. 77, 313-38
4. DNA ligases: structure, reaction mechanism, and function. Chem. Rev. 106, 687-99
5. Ku80- and DNA ligase IV-deficient plants are sensitive to ionizing radiation and defective in T-DNA integration. Plant J. 34, 427-40
6. Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence. Radiother Oncol 92, 310-5
7. Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells. Nucleic Acids Res. 29, 1653-60