DNA Ligase: Structure, Mechanism, and Function

@article{Lehnman1974DNALS,
  title={DNA Ligase: Structure, Mechanism, and Function},
  author={I. R. Lehnman},
  journal={Science},
  year={1974},
  volume={186},
  pages={790 - 797}
}
DNA ligase of E. coli is a polypeptide of molecular weight 75,000. The comparable T4-induced enzyme is somewhat smaller (63,000 to 68,000). Both enzymes catalyze the synthesis of phosphodiester bonds between adjacent 5'-phosphoryl and 3'-hydroxyl groups in nicked duplex DNA, coupled to the cleavage of the pyrophosphate bond of DPN (E. coli) or ATP (T4). Phosphodiester bond synthesis catalyzed by both enzymes occurs in a series of these discrete steps and involves the participation of two… Expand
Structure of the adenylation domain of an NAD+-dependent DNA ligase.
TLDR
Comparison of the structure of the NAD+4-dependent DNA ligase with that of ATP-dependent ligases and mRNA-capping enzymes demonstrates the manifold utilisation of a conserved nucleotidyltransferase domain within this family of enzymes. Expand
Multiple roles of DNA ligase at the replication fork.
The loss of superhelical turns from a covalently closed duplex DNA exposed to bacteriophage T4 DNA ligase in the presence of AMP and Mg2+ has recently been found to be gradual and not suddenExpand
Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates.
TLDR
It is suggested that these results will enable the assembly of TNA oligonucleotides of lengths beyond what is currently possible by solid-phase synthesis and provide a starting point for further optimization by directed evolution. Expand
A high-throughput assay for the adenylation reaction of bacterial DNA ligase.
TLDR
A high-throughput assay that measures the adenylation reaction specifically by monitoring ligase-AMP formation via scintillation proximity technologies and certain adenosine analogs were found to inhibit the adanylation assay and had similar potency of inhibition in a DNA ligation assay. Expand
Functional domains of an ATP-dependent DNA ligase.
TLDR
The crystal structure of an ATP-dependent DNA ligase from bacteriophage T7 revealed that the protein comprised two structural domains, and overexpressed them separately and purified them to homogeneity suggest that the specificity of DNA ligases for nick sites in DNA is produced by a combination of these different DNA binding activities in the intact enzyme. Expand
Kinetic Mechanism of Human DNA Ligase I Reveals Magnesium-dependent Changes in the Rate-limiting Step That Compromise Ligation Efficiency*
TLDR
The kinetic and thermodynamic framework that is determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases. Expand
Identification of essential residues in Thermus thermophilus DNA ligase.
TLDR
Evidence indicates that a previously identified KXDG motif for adenylation of eukaryotic DNA ligases is also the adenYLation site for NAD+-dependent bacterial DNA ligase, and it is demonstrated that mutations at a different Lys residue, K294, may modulate the fidelity of Tth DNA lig enzyme. Expand
Rapid Time Scale Analysis of T4 DNA Ligase-DNA Binding.
TLDR
The observations demonstrate the mechanistic underpinnings of competitive inhibition by rapid binding of nonsubstrate DNA, and of substrate inhibition by blocking of the self-adenylylation reaction through nick binding by deadenylylated ligase, and reveal that product release is not the rate-determining step in turnover. Expand
Crystal Structure and Nonhomologous End-joining Function of the Ligase Component of Mycobacterium DNA Ligase D*
TLDR
It is surmise that the signature error-prone quality of bacterial NHEJ in vivo arises from a dynamic balance between the end-remodeling and end-sealing steps. Expand
ATP-dependent DNA ligase from Archaeoglobus fulgidus displays a tightly closed conformation.
TLDR
The crystal structure of an ATP-dependent DNA ligase from Archaeoglobus fulgidus has been determined in the DNA-unbound unadenylated state and resembles the closed conformation of P. furiosusDNA ligase but was even more closed, thus enhancing the understanding of the conformational variability of these enzymes. Expand
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References

SHOWING 1-4 OF 4 REFERENCES
Synthetic fuels for automotive transportation,:' paper presented at the spring meeting of the Combustion Institute
  • 1974
Jencks, Catalysis in Chemistry and Enzymology (McGraw-Hill
  • New York,
  • 1969
Support for the research on DNA ligase performed in my laboratory was provided by NIH research grant GM-06196
    and C
    • C. Richardson, ibid., p.