Reaction: ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate (overall reaction)
(1a) ATP + [DNA ligase]-L-lysine = [DNA ligase]-N6-(5'-adenylyl)-L-lysine + diphosphate
(1b) [DNA ligase]-N6-(5'-adenylyl)-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
(1c) (deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
Other name(s): polydeoxyribonucleotide synthase (ATP); polynucleotide ligase (ambiguous); sealase; DNA repair enzyme (ambiguous); DNA joinase (ambiguous); DNA ligase (ambiguous); deoxyribonucleic ligase (ambiguous); deoxyribonucleate ligase (ambiguous); DNA-joining enzyme (ambiguous); deoxyribonucleic-joining enzyme (ambiguous); deoxyribonucleic acid-joining enzyme (ambiguous); deoxyribonucleic repair enzyme (ambiguous); deoxyribonucleic joinase (ambiguous); deoxyribonucleic acid ligase (ambiguous); deoxyribonucleic acid joinase (ambiguous); deoxyribonucleic acid repair enzyme (ambiguous); poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)
Systematic name: poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (ATP)
Comments: The enzyme catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by ATP, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.2, DNA ligase (NAD+), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9015-85-4
References:
1. Becker, A., Lyn, G., Gefter, M. and Hurwitz, J. The enzymatic repair of DNA. II. Characterization of phage-induced sealase. Proc. Natl. Acad. Sci. USA 58 (1967) 1996-2003. [PMID: 4295584]
2. Bertazzoni, U., Mathelet, M. and Campagnari, F. Purification and properties of a polynucleotide ligase from calf thymus glands. Biochim. Biophys. Acta 287 (1972) 404-414. [PMID: 4641251]
3. Weiss, B. and Richardson, C.C. Enzymatic breakage and joining of deoxyribonucleic acid. I. Repair of single-strand breaks in DNA by an enzyme system from Escherichia coli infected with T4 bacteriophage. Proc. Natl. Acad. Sci. USA 57 (1967) 1021-1028. [PMID: 5340583]
4. Howes, T.R. and Tomkinson, A.E. DNA ligase I, the replicative DNA ligase. Subcell. Biochem. 62 (2012) 327-341. [PMID: 22918593]