scholarly journals XRCC1 Polypeptide Interacts with DNA Polymerase   and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular 'Nick-Sensor' In Vitro

1996 ◽  
Vol 24 (22) ◽  
pp. 4387-4394 ◽  
Author(s):  
K. W. Caldecott ◽  
S. Aoufouchi ◽  
P. Johnson ◽  
S. Shall
Keyword(s):  
Dna Polymerase ◽  
Dna Ligase ◽  
Dna Ligase Iii

scholarly journals A novel interaction between DNA ligase III and DNA polymerase γ plays an essential role in mitochondrial DNA stability

2007 ◽  
Vol 402 (1) ◽  
pp. 175-186 ◽  
Author(s):  
Ananya De ◽  
Colin Campbell
Keyword(s):  
Mitochondrial Dna ◽  
Dna Polymerase ◽  
Mitochondrial Protein ◽  
Dna Ligase ◽  
Zinc Finger Domain ◽  
Wild Type ◽  
Mitochondrial Dna Copy Number ◽  
Dna Polymerase Γ ◽  
Dna Ligase Iii

The data in the present study show that DNA polymerase γ and DNA ligase III interact in mitochondrial protein extracts from cultured HT1080 cells. An interaction was also observed between the two recombinant proteins in vitro. Expression of catalytically inert versions of DNA ligase III that bind DNA polymerase γ was associated with reduced mitochondrial DNA copy number and integrity. In contrast, overexpression of wild-type DNA ligase III had no effect on mitochondrial DNA copy number or integrity. Experiments revealed that wild-type DNA ligase III facilitates the interaction of DNA polymerase γ with a nicked DNA substrate in vitro, and that the zinc finger domain of DNA ligase III is required for this activity. Mitochondrial protein extracts prepared from cells overexpressing a DNA ligase III protein that lacked the zinc finger domain had reduced base excision repair activity compared with extracts from cells overexpressing the wild-type protein. These data support the interpretation that the interaction of DNA ligase III and DNA polymerase γ is required for proper maintenance of the mammalian mitochondrial genome.

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.

scholarly journals DNA ligase I variants fail in the ligation of mutagenic repair intermediates with mismatches and oxidative DNA damage

Mutagenesis ◽  
2020 ◽  
Author(s):  
Qun Tang ◽  
Pradnya Kamble ◽  
Melike Çağlayan
Keyword(s):  
Dna Polymerase ◽  
Oxidative Dna Damage ◽  
Deficiency Syndrome ◽  
Dna Ligase ◽  
Synonymous Mutations ◽  
Dna Ligase I ◽  
Dna Replication And Repair ◽  
Dna Mismatches ◽  
Dna Strand

Abstract DNA ligase I (LIG1) joins DNA strand breaks during DNA replication and repair transactions and contributes to genome integrity. The mutations (P529L, E566K, R641L and R771W) in LIG1 gene are described in patients with LIG1-deficiency syndrome that exhibit immunodeficiency. LIG1 senses 3’-DNA ends with a mismatch or oxidative DNA base inserted by a repair DNA polymerase. However, the ligation efficiency of the LIG1 variants for DNA polymerase-promoted mutagenesis products with 3’-DNA mismatches or 8-oxo-2’-deoxyguanosine (8-oxodG) remains undefined. Here, we report that R641L and R771W fail in the ligation of nicked DNA with 3’-8-oxodG, leading to an accumulation of 5’-AMP-DNA intermediates in vitro. Moreover, we found that the presence of all possible 12 non-canonical base pairs variously impacts the ligation efficiency by P529L and R771W depending on the architecture at the DNA end, whereas E566K exhibits no activity against all substrates tested. Our results contribute to the understanding of the substrate specificity and mismatch discrimination of LIG1 for mutagenic repair intermediates and the effect of non-synonymous mutations on ligase fidelity.

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.

scholarly journals The human checkpoint sensor and alternative DNA clamp Rad9–Rad1–Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery

2005 ◽  
Vol 389 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Ekaterina SMIRNOVA ◽  
Magali TOUEILLE ◽  
Enni MARKKANEN ◽  
Ulrich HÜBSCHER
Keyword(s):  
Quality Control ◽  
Dna Polymerase ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Ligase ◽  
Dna Polymerase Β ◽  
Flap Endonuclease 1 ◽  
Important Target ◽  
Dna Ligase I ◽  
Base Excision

The human checkpoint sensor and alternative clamp Rad9–Rad1–Hus1 can interact with and specifically stimulate DNA ligase I. The very recently described interactions of Rad9–Rad1–Hus1 with MutY DNA glycosylase, DNA polymerase β and Flap endonuclease 1 now complete our view that the long-patch base excision machinery is an important target of the Rad9–Rad1–Hus1 complex, thus enhancing the quality control of DNA.

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