Human DNA ligase I completely encircles and partially unwinds nicked DNA

Nature ◽  
2004 ◽  
Vol 432 (7016) ◽  
pp. 473-478 ◽  
Author(s):  
John M. Pascal ◽  
Patrick J. O'Brien ◽  
Alan E. Tomkinson ◽  
Tom Ellenberger
Keyword(s):  
Dna Ligase ◽  
Human Dna ◽  
Dna Ligase I

scholarly journals Thermodynamics of Human DNA Ligase I Trimerization and Association with DNA Polymerase β

1998 ◽  
Vol 273 (32) ◽  
pp. 20540-20550 ◽  
Author(s):  
Emilios K. Dimitriadis ◽  
Rajendra Prasad ◽  
Mary K. Vaske ◽  
Ling Chen ◽  
Alan E. Tomkinson ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Dna Ligase ◽  
Dna Polymerase Β ◽  
Human Dna ◽  
Dna Ligase I

scholarly journals Late induction of human DNA ligase I after UV-C irradiation

1995 ◽  
Vol 23 (6) ◽  
pp. 962-966 ◽  
Author(s):  
Alessandra Montecucco ◽  
Elena Savini ◽  
Giuseppe Biamonti ◽  
Miria Stefanini ◽  
Federico Focher ◽  
...  
Keyword(s):  
Dna Ligase ◽  
Human Dna ◽  
Dna Ligase I ◽  
Uv C

scholarly journals Natural-product inhibitors of human DNA ligase I

1996 ◽  
Vol 314 (3) ◽  
pp. 993-1000 ◽  
Author(s):  
Ghee T. TAN ◽  
Sangkook LEE ◽  
Ik-Soo LEE ◽  
Jingwen CHEN ◽  
Pete LEITNER ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Natural Product ◽  
Conformational Changes ◽  
Enzyme Inhibitor ◽  
Enzymic Activity ◽  
Dna Ligase ◽  
Enzyme Active Site ◽  
Dna Relaxation ◽  
Human Dna ◽  
Dna Ligase I

Enzymic activity mediated by recombinant human DNA ligase I (hLI), in conjunction with tannin removal procedures, has been applied to a natural-product screen involving ~1000 plant extracts and various pure compounds. The primary hLI activity assay involved the measurement of the amount of radiolabelled phosphate in a synthetic nucleic acid hybrid that becomes resistant to alkaline phosphatase as a result of ligation. A bioactivity-guided fractionation scheme resulted in the isolation of ursolic [IC50 = 100 μg/ml (216 μM)] and oleanolic [IC50 = 100 μg/ml (216 μM)] acids from Tricalysia niamniamensis Hiern (Rubiaceae), which demonstrated similar DNA ligase inhibition profiles to other triterpenes such as aleuritolic acid. Protolichesterinic acid [IC50 = 6 μg/ml (20 μM)], swertifrancheside [IC50 = 8 μg/ml (11 μM)] and fulvoplumierin [IC50 = 87 μg/ml (357 μM)] represent three additional natural-product structural classes that inhibit hLI. Fagaronine chloride [IC50 = 10 μg/ml (27 μM)] and certain flavonoids are also among the pure natural products that were found to disrupt the activity of the enzyme, consistent with their nucleic acid intercalative properties. Further analyses revealed that some of the hLI-inhibitory compounds interfered with the initial adenylation step of the ligation reaction, indicating a direct interaction with the enzyme protein. However, in all cases, this enzyme–inhibitor interaction did not disrupt the DNA relaxation activity mediated by hLI. These results indicate that, although the same enzyme active site may be involved in both enzyme adenylation and DNA relaxation, inhibitors may exert allosteric effects by inducing conformational changes that disrupt only one of these activities. Studies with inhibitors are important for the assignment of specific cellular functions to these enzymes, as well as for their development into clinically useful antitumour agents.

Polymorphisms in the human DNA ligase I gene (LIG1) including a complex GT repeat

1998 ◽  
Vol 406 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Kenneth J Livak ◽  
Wayne A Little ◽  
Sylvia L Stack ◽  
Thomas A Patterson
Keyword(s):  
Dna Ligase ◽  
Human Dna ◽  
Dna Ligase I ◽  
I Gene

Discovery of monocarbonyl curcumin hybrids as a novel class of human DNA ligase I inhibitors: in silico design, synthesis and biology

RSC Advances ◽  
2016 ◽  
Vol 6 (31) ◽  
pp. 26003-26018 ◽  
Author(s):  
Dhanaraju Mandalapu ◽  
Deependra Kumar Singh ◽  
Sonal Gupta ◽  
Vishal M. Balaramnavar ◽  
Mohammad Shafiq ◽  
...  
Keyword(s):  
In Silico ◽  
Pharmacophore Model ◽  
Dna Ligase ◽  
Design Synthesis ◽  
In Silico Design ◽  
Human Dna ◽  
Dna Ligase I

A pharmacophore model identified a novel class of hLigI inhibitors to treat cancer. 36 compounds were synthesized and the identified inhibitor, compound 23 shown antiligase activity at IC50 24.9 μM by abolishing the interaction between hLigI and DNA.

scholarly journals Phosphorylation of Serine 51 Regulates the Interaction of Human DNA Ligase I with Replication Factor C and Its Participation in DNA Replication and Repair

2012 ◽  
Vol 287 (44) ◽  
pp. 36711-36719 ◽  
Author(s):  
Zhimin Peng ◽  
Zhongping Liao ◽  
Barbara Dziegielewska ◽  
Yoshi Matsumoto ◽  
Stefani Thomas ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Ligase ◽  
Replication Factor C ◽  
Replication Factor ◽  
Human Dna ◽  
Dna Ligase I ◽  
Dna Replication And Repair ◽  
Factor C
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