Disease relevance of Lig1

• DNA ligase and DNase activities in mouse erythroleukemia cells during dimethyl sulfoxide-induced differentiation [1].
• Rapidly dividing cells (mouse ascites tumor cells and calf thymus) contain higher amounts of DNA ligase I than other cells (calf liver and spleen, human placenta, and rabbit spleen), while no such correlation was observed for DNA ligase II [2].
• DNA ligase activity cosedimented with mature polyomavirus minichromosomes [3].
• Benzamide potentiation of the cytotoxicity of bifunctional galactitol [correction of galacticol] in resistant P388 leukemia correlates with inhibition of DNA ligase II [4].
• DNA ligase from mouse Ehrlich ascites tumor cells [5].

High impact information on Lig1

• Evidence has indicated that DNA ligase I is central to DNA replication, as well as being involved in DNA repair processes [6].
• It has been reported that DNA ligase I is essential for cell viability, but here we show that cells lacking DNA ligase I are in fact viable [6].
• A patient with altered DNA ligase I displayed a phenotype similar to Bloom's syndrome, being immunodeficient, growth retarded and predisposed to cancer [6].
• DNA ligase I is required for fetal liver erythropoiesis but is not essential for mammalian cell viability [6].
• Thus, DNA ligases II and III are not redundant with DNA ligase I for the function(s) associated with cell proliferation [7].

Chemical compound and disease context of Lig1

• DNA ligase and DNase levels were measured in cell-free extracts from untreated mouse erythroleukemia (MEL) cells and from cells treated with dimethyl sulfoxide (Me2SO) to induce erythroid differentiation [1].

Biological context of Lig1

• DNA ligase I null fibroblasts from Lig1 mutant embryos showed an accumulation of DNA replication intermediates and increased genome instability [8].
• To address this issue, we generated a second Lig1 targeted allele and found that the phenotypes of our two Lig1 mutant mouse lines are identical [8].
• The results demonstrate that Lig1 is expressed in the liver during active cell proliferation [9].
• A different minigene, under the control of the mouse HPRT promoter and embedded in its natural CpG-rich island, overcame this position effect and was stably expressed when targeted to the identical site in the Lig1 locus [10].
• The level of genome instability was significantly elevated in the spleens of DNA ligase I mutant mice and, because we have found no evidence for any DNA repair defect associated with DNA ligase I deficiency, we believe that this may result directly from the accumulation of replication intermediates [11].

Anatomical context of Lig1

• In addition, Lig1 expression was analyzed during the course of mouse liver-cell regeneration induced by partial hepatectomy, necrogenic doses of carbon tetrachloride, or the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene [9].
• Lig1 reacted with all NK cells in polyclonal NK populations from different donors, demonstrating that all NK cells express at least one KIR2D receptor [12].
• A 3172-nucleotide (nt) cDNA clone encoding mouse DNA ligase I (LigI) was isolated from an embryonic stem cell cDNA library [13].
• The major ligase activity present in calf thymus cell extracts, DNA ligase I, has been purified 1000-fold [2].
• RESULTS: The amount of DNA ligase I enzyme in malignant tumors was considerably higher than that in benign normal tissues and peripheral blood lymphocytes [14].

Associations of Lig1 with chemical compounds

• Integrin engagement also inhibited increases in gammaH2AX in BLM-treated cells transfected with Lig1 siRNA [15].
• Inhibitors were chosen for selectivity toward DNA polymerase alpha (aphidicolin, myricetin), DNA ligase (ethidium bromide), or multiple repair enzymes (ara-C, doxorubicin) [16].
• It seems that by increasing DNA ligase I levels these cells can survive DNA damage in the presence of 3-aminobenzamide [17].

Other interactions of Lig1

• The activities of poly (ADP-ribose) polymerase (PARP), DNA polymerase b and DNA ligase in fibrosarcoma, lymphosarcoma and ascites recorded varying degrees of increase following gamma irradiation (2 Gy) [18].
• Specific assays for DNA topoisomerase II and DNA ligase activity were carried out on each fraction [3].
• Proteins and enzymatic activities associated with this mouse cell multiprotein form of DNA polymerase include the DNA polymerases alpha and delta, DNA primase, proliferating cell nuclear antigen (PCNA), DNA ligase I, DNA helicase, and DNA topoisomerases I and II [19].

Analytical, diagnostic and therapeutic context of Lig1

• Using gene targeting in embryonic stem (ES) cells, we have produced DNA ligase I-deficient mice [6].
• Cloning and sequence analysis of a cDNA coding for the murine DNA ligase I enzyme [20].
• Using gel filtration of whole cell extracts prepared at physiological salt conditions (0.15 M NaCl), we find no evidence for a stable preexisting complex of DNA Pol beta with the DNA ligase IIIalpha-XRCC1 heterodimer [21].
• EXPERIMENTAL DESIGN: DNA ligase I level was measured by Western immunoblot assay in various human malignant tumor specimens and benign tissues obtained from patients, in peripheral blood lymphocytes obtained from healthy donors, and in human tumors grown in nude mice [14].
• We have developed the single-strand linker ligation method (SSLLM), which uses DNA ligase to add a dsDNA linker to single-stranded (ss) full-length cDNA [22].

References