scholarly journals DNA-ligase activity in axolotl early development: evidence for a multilevel regulation of gene expression

Development ◽  
1986 ◽  
Vol 97 (Supplement) ◽  
pp. 85-95
Author(s):  
J. Signoret ◽  
J. C. David
Keyword(s):  
Molecular Form ◽  
Regulation Of Gene Expression ◽  
Molecular Forms ◽  
Dna Ligase ◽  
Amphibian Embryo ◽  
Dna Ligases ◽  
Level Of Activity ◽  
Dna Ligase I ◽  
Basic Features ◽  
Multilevel Regulation

DNA-ligase activity in eukaryotic cells is carried out by two different molecular forms of the enzyme. This molecular duality, first described in mammals (Söderhäll & Lindhal, 1973), has been reported in chicken (David, 1977), amphibians (Carré, Signoret, Lefresne & David, 1981), fish, sea urchin and crab (Signoret & David, 1986). Depending on the developmental stage and the tissue considered, types of cell are available that express exclusively either one or the other of the two DNA-ligases with a defined level of activity. DNA-ligase I and DNA-ligase II, encoded by distinct structural genes (Thiebaud et al. 1985), can be unambiguously characterized and the advantages offered by the early amphibian embryo have made possible the identification of some basic features of their regulation. The Gene for DNA-ligase I exists in two Regulated States The heavy molecular form of the enzyme, referred to as DNA-ligase I, is generally present in proliferating tissues.

MAMMALIAN DNA LIGASES; ALTERED DNA LIGASE I IN BLOOM'S SYNDROME

1991 ◽  
pp. 71
Author(s):  
ALAN E. TOMKINSON ◽  
DEBORAH E. BARNES ◽  
KEN-ICHI KODAMA ◽  
EEMA ROBERTS ◽  
GRAHAM DALY ◽  
...  
Keyword(s):  
Dna Ligase ◽  
Bloom's Syndrome ◽  
Dna Ligases ◽  
Bloom’S Syndrome ◽  
Dna Ligase I

scholarly journals The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates

2020 ◽  
Vol 48 (7) ◽  
pp. 3708-3721 ◽  
Author(s):  
Melike Çağlayan
Keyword(s):  
Excision Repair ◽  
Dna Ligase ◽  
Active Site Residues ◽  
Dna Ligases ◽  
Terminal Domain ◽  
Dna Ligase I ◽  
Nucleotide Insertion ◽  
Base Excision ◽  
Ligation Step

Abstract DNA ligase I and DNA ligase III/XRCC1 complex catalyze the ultimate ligation step following DNA polymerase (pol) β nucleotide insertion during base excision repair (BER). Pol β Asn279 and Arg283 are the critical active site residues for the differentiation of an incoming nucleotide and a template base and the N-terminal domain of DNA ligase I mediates its interaction with pol β. Here, we show inefficient ligation of pol β insertion products with mismatched or damaged nucleotides, with the exception of a Watson–Crick-like dGTP insertion opposite T, using BER DNA ligases in vitro. Moreover, pol β N279A and R283A mutants deter the ligation of the promutagenic repair intermediates and the presence of N-terminal domain of DNA ligase I in a coupled reaction governs the channeling of the pol β insertion products. Our results demonstrate that the BER DNA ligases are compromised by subtle changes in all 12 possible noncanonical base pairs at the 3′-end of the nicked repair intermediate. These findings contribute to understanding of how the identity of the mismatch affects the substrate channeling of the repair pathway and the mechanism underlying the coordination between pol β and DNA ligase at the final ligation step to maintain the BER efficiency.

scholarly journals Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination.

1995 ◽  
Vol 15 (6) ◽  
pp. 3206-3216 ◽  
Author(s):  
Y F Wei ◽  
P Robins ◽  
K Carter ◽  
K Caldecott ◽  
D J Pappin ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cdna Clone ◽  
Dna Ligase ◽  
Dna Ligases ◽  
Dna Ligase Iv ◽  
Ligase Iv ◽  
Dna Ligase I ◽  
Cloned Cdna ◽  
Dna Ligase Iii

Three distinct DNA ligases, I to III, have been found previously in mammalian cells, but a cloned cDNA has been identified only for DNA ligase I, an essential enzyme active in DNA replication. A short peptide sequence conserved close to the C terminus of all known eukaryotic DNA ligases was used to search for additional homologous sequences in human cDNA libraries. Two different incomplete cDNA clones that showed partial homology to the conserved peptide were identified. Full-length cDNAs were obtained and expressed by in vitro transcription and translation. The 103-kDa product of one cDNA clone formed a characteristic complex with the XRCC1 DNA repair protein and was identical with the previously described DNA ligase III. DNA ligase III appears closely related to the smaller DNA ligase II. The 96-kDa in vitro translation product of the second cDNA clone was also shown to be an ATP-dependent DNA ligase. A fourth DNA ligase (DNA ligase IV) has been purified from human cells and shown to be identical to the 96-kDa DNA ligase by unique agreement between mass spectrometry data on tryptic peptides from the purified enzyme and the predicted open reading frame of the cloned cDNA. The amino acid sequences of DNA ligases III and IV share a related active-site motif and several short regions of homology with DNA ligase I, other DNA ligases, and RNA capping enzymes. DNA ligases III and IV are encoded by distinct genes located on human chromosomes 17q11.2-12 and 13q33-34, respectively.

Identification of a novel human DNA ligase I inhibitor that promotes cellular apoptosis in DLD-1 cells: an in silico and in vitro mechanistic study

RSC Advances ◽  
2016 ◽  
Vol 6 (97) ◽  
pp. 94574-94587 ◽  
Author(s):  
Deependra Kumar Singh ◽  
Mohd. Kamil Hussain ◽  
Shagun Krishna ◽  
Amit Laxmikant Deshmukh ◽  
Mohammad Shameem ◽  
...  
Keyword(s):  
In Silico ◽  
Specific Inhibitor ◽  
Mechanistic Study ◽  
Dna Ligase ◽  
Dna Ligases ◽  
Human Dna ◽  
Dna Ligase I ◽  
Cellular Apoptosis

The compound S-097/98 is a specific inhibitor of hLig1. As shown in the figure, the compound inhibits only hLig1 while other human and non-human DNA ligases are not inhibited.

scholarly journals Mammalian DNA ligases. Catalytic domain and size of DNA ligase I.

1990 ◽  
Vol 265 (21) ◽  
pp. 12611-12617 ◽  
Author(s):  
A E Tomkinson ◽  
D D Lasko ◽  
G Daly ◽  
T Lindahl
Keyword(s):  
Catalytic Domain ◽  
Dna Ligase ◽  
Dna Ligases ◽  
Dna Ligase I

Tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can specifically target bacterial DNA ligases and can distinguish them from human DNA ligase I

2015 ◽  
Vol 13 (19) ◽  
pp. 5475-5487 ◽  
Author(s):  
Nisha Yadav ◽  
Taran Khanam ◽  
Ankita Shukla ◽  
Niyati Rai ◽  
Kanchan Hajela ◽  
...  
Keyword(s):  
Dna Ligase ◽  
Indole Derivatives ◽  
Dna Metabolism ◽  
Bacterial Dna ◽  
Dna Ligases ◽  
Human Dna ◽  
Dna Ligase I ◽  
Critical Components

DNA ligases are critical components for DNA metabolism in all organisms.

scholarly journals Mammalian DNA ligases. Biosynthesis and intracellular localization of DNA ligase I.

1990 ◽  
Vol 265 (21) ◽  
pp. 12618-12622
Author(s):  
D D Lasko ◽  
A E Tomkinson ◽  
T Lindahl
Keyword(s):  
Intracellular Localization ◽  
Dna Ligase ◽  
Dna Ligases ◽  
Dna Ligase I

scholarly journals DNA ligase I mediates essential functions in mammalian cells.

1995 ◽  
Vol 15 (8) ◽  
pp. 4303-4308 ◽  
Author(s):  
J H Petrini ◽  
Y Xiao ◽  
D T Weaver
Keyword(s):  
Mammalian Cells ◽  
Catalytic Domain ◽  
Embryonic Stem ◽  
Dna Ligase ◽  
Null Mutation ◽  
Dna Ligases ◽  
Dna Ligase I ◽  
The Creation ◽  
Stem Cell Lines

DNA replication, repair, and recombination are essential processes in mammalian cells. Hence, the application of gene targeting to the study of these DNA metabolic pathways requires the creation of nonnull mutations. We have developed a method for introducing partially defective mutants in murine embryonic stem cells that circumvents the problem of cellular lethality of targeted mutations at essential loci. Using this approach, we have determined that mammalian DNA ligase I is essential for cell viability. Thus, DNA ligases II and III are not redundant with DNA ligase I for the function(s) associated with cell proliferation. Partial complementation of the lethal DNA ligase I null mutation allowed the creation of deficient embryonic stem cell lines. We found that a wild-type DNA ligase I cDNA, as well as a variant DNA ligase I cDNA, was able to rescue the lethality of the homozygous null mutation, whereas an N-terminal deletion mutant consisting of the minimal DNA ligase I catalytic domain was not. This observation demonstrates that sequences outside the DNA ligase I catalytic domain are essential for DNA ligase I function in vivo.

scholarly journals Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination.

1995 ◽  
Vol 15 (10) ◽  
pp. 5412-5422 ◽  
Author(s):  
J Chen ◽  
A E Tomkinson ◽  
W Ramos ◽  
Z B Mackey ◽  
S Danehower ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Chromosome 17 ◽  
Dna Ligase ◽  
Cdna Clones ◽  
Dna Ligases ◽  
Cell Extracts ◽  
Human Dna ◽  
Dna Ligase I ◽  
Dna Ligase Iii

Three biochemically distinct DNA ligase activities have been identified in mammalian cell extracts. We have recently purified DNA ligase II and DNA ligase III to near homogeneity from bovine liver and testis tissue, respectively. Amino acid sequencing studies indicated that these enzymes are encoded by the same gene. In the present study, human and murine cDNA clones encoding DNA ligase III were isolated with probes based on the peptide sequences. The human DNA ligase III cDNA encodes a polypeptide of 862 amino acids, whose sequence is more closely related to those of the DNA ligases encoded by poxviruses than to replicative DNA ligases, such as human DNA ligase I. In vitro transcription and translation of the cDNA produced a catalytically active DNA ligase similar in size and substrate specificity to the purified bovine enzyme. The DNA ligase III gene was localized to human chromosome 17, which eliminated this gene as a candidate for the cancer-prone disease Bloom syndrome that is associated with DNA joining abnormalities. DNA ligase III is ubiquitously expressed at low levels, except in the testes, in which the steady-state levels of DNA ligase III mRNA are at least 10-fold higher than those detected in other tissues and cells. Since DNA ligase I mRNA is also present at high levels in the testes, we examined the expression of the DNA ligase genes during spermatogenesis. DNA ligase I mRNA expression correlated with the contribution of proliferating spermatogonia cells to the testes, in agreement with the previously defined role of this enzyme in DNA replication. In contrast, elevated levels of DNA ligase III mRNA were observed in primary spermatocytes undergoing recombination prior to the first meiotic division. Therefore, we suggest that DNA ligase III seals DNA strand breaks that arise during the process of meiotic recombination in germ cells and as a consequence of DNA damage in somatic cells.

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