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DNA-Binding Proteins and DNA-Synthesizing Enzymes in Eukaryotes
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
Mammalian cells contain at least three distinct DNA polymerases, i.e., DNA polymerases α, β, and γ Experimental evidence suggests that DNA polymerase α is responsible for DNA replication and DNA polymerase β seems to be involved in DNA repair. DNA polymerase γ is required in mitochondrial DNA replication. However, the role of nuclear DNA polymerase γ is still unknown. The infidelity of DNA polymerase α in DNA synthesis was demonstrated in malignant cells and cells induced by carcinogens. Chromosome duplication is discontinuous in nature. DNA ligases join the intermediate fragments to high molecular DNA. DNA-binding proteins unwind DNA helix, while others bind to the single-stranded DNA and even stimulate homologous DNA polymerase activities.
Role of Nonhistone Chromosomal Proteins in Selective Gene Expression
Published in Gerald M. Kolodny, Eukaryotic Gene Regulation, 2018
I.R. Phillips, E.A. Shephard, J.L. Stein, G.S. Stein
Specific DNA-binding nonhistone proteins have been isolated by several groups of workers, and the techniques used, together with their associated problems, were described in the section on fractionating the nonhistone chromosomal proteins by DNA affinity techniques. In this section, we will discuss some of the properties of these DNA-binding proteins which may have a bearing on their postulated role in the control of gene expression.
Embryology
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Transcription factors constitute another important group of signaling molecules. These DNA-binding proteins are involved in regulating gene expression. Examples of transcription factors closely involved in nephrogenesis include the gene products of the Pax2 gene and Wilms’ tumor suppressor gene (WT1 gene), both of which play a central role in branching of the ureteric bud and in the induction of metanephric mesenchyme. Other signaling molecules include those responsible for cell-to-cell adhesion and cell-to-cell matrix adhesion, such as laminins and integrins.
Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors
Published in Annals of Medicine, 2023
Moustafa M. Madkour, Wafaa S. Ramadan, Ekram Saleh, Raafat El-Awady
DNA methylation is known to affect the interaction with certain DNA-binding proteins including DNA Tops. The role of DNA methylation in controlling the response of cancer cells to drugs including Top I inhibitors was identified by the use of the hypomethylating cytidine analogue 5-azacytidine (5-azaC). The pre-treatment of Chinese hamster ovary cells with 5-azaC was demonstrated to increase their sensitivity to CPT and to result in a strong synergistic effect on chromosomal damage. This could be premised on the idea that changing chromosome replication timing after DNA hypomethylation increases the number of replication forks in early S phase, which subsequently increases the likelihood of collision between a blocked DNA-Top I-CPT cleavage complex and the replication fork [61]. In addition, the cytotoxicity of irinotecan was demonstrated to be increased by 5-azaC in colorectal cancer cells via at least one of the following mechanisms: (a) demethylation of the Top I promoter, (b) indirect stimulation of Top I expression, and (c) amendment of cell cycle progression and/or apoptosis following DNA damage [62,63] (Figure 2(A)). Interestingly, the combination of 5-azaC and irinotecan resulted in a synergistic response with considerable improvement in survival and tumor regression in human colon cancer xenograft mice [64,65]. In pheochromocytoma/paraganglioma, the intermittent coadministration of 5-azaC also increased the efficacy of low doses of CPT and other Top I inhibitors in in vitro and in vivo settings [66].
DNA analysis of low- and high-density fractions defines heterogeneous subpopulations of small extracellular vesicles based on their DNA cargo and topology
Published in Journal of Extracellular Vesicles, 2019
Elisa Lázaro-Ibáñez, Cecilia Lässer, Ganesh Vilas Shelke, Rossella Crescitelli, Su Chul Jang, Aleksander Cvjetkovic, Anaís García-Rodríguez, Jan Lötvall
Notably, the DNA fragments identified in most of the gradient fractions had characteristic peaks around 180, 360, and 540 bp (most clearly visible in F5 from HMC-1 and F3 from TF-1, Figure 1(f)) resembling those of nucleosomes (DNA wrapped around histone proteins). Interestingly, the proteomic analysis of HMC-1 fractions showed the presence of notably more DNA-binding proteins in the HD fractions (8.9% of the proteins) compared to the LD fractions (5.9% of the proteins) (Figure 2(a)). As shown in the Venn diagram (Figure 2(b)), 72 DNA-binding proteins were identified in both preparations, whereas 36 and 58 proteins were only detected in LD and HD HMC-1 fractions, respectively. Analysing the DNA binding proteins in more detail, the HD fractions were found to contain more DNA-binding histone proteins, including the core histones H2A, H2B, H3, and H4 that form the nucleosome and the linker histone H1 (Figure 2(c)). These results were validated by Western blotting, confirming that DNA-binding histones H2A and H3 were mainly associated with HD fractions rather than LD sEVs (Figure 2(d)). Overall, characteristic DNA profiles of nucleosomal DNA were detected in most of the fractions. Mass spectrometry and Western blotting confirmed the enrichment of DNA binding proteins, including core and linker histones, in the HD fractions that contained most of the DNA. However, the same proteins were limited in number or absent in the LD fractions, which contained less DNA.
Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Mohammad Hadi Nematollahi, Masoud Torkzadeh-Mahanai, Abbas Pardakhty, Hossein Ali Ebrahimi Meimand, Gholamreza Asadikaram
EtBr is a universal DNA intercalation dye and its fluorescence intensity increases substantially after binding to DNA. In the presence of another molecule, there would be competition between the new molecule and EtBr for binding to DNA. Such competitive binding studies have been used to identify the new DNA binding protein or drug. Our result confirmed that NMM similar to protamine has the ability to displace EtBr (Figure 4). Therefore, NMM protein is likely to be an intercalator of DNA. Although, the NMM was also able to induce a decrease in EtBr fluorescence but this effect was more obvious in presence of protamine. Similar results regarding protamine EtBr exclusion are also reported by De Ilarduya et al. [39].