Transcriptionally Regulatory Sequences of Phylogenetic Significance
S. K. Dutta in DNA Systematics, 2019
While a double-stranded DNA assumes helical conformation, its topology changes upon complexing with proteins as in the case of nucleosome formation involving the histones. Certain sequences of DNA bend into a complete circle in the space of about 80 bp,186 which is only one half of the persistent length in solution. Bends and kinks occur frequently in native trypanosome kinetoplast DNA for sequences consisting of C(A)5-6T repeats at 10 bp apart, in phase with the helical periodicity.187 It is suspected that altered DNA conformations per se serve as signals for protein recognition.188,189 Conversely, the binding of proteins, e.g., CAP, can induce DNA bending several bases toward the promoter sites located within the center of symmetry for binding. This supports the notion that DNA topology can be altered in such an effective way that the stabilization of RNA polymerase is favored and transcription promoted.190–192 It is well recognized that initiation of transcription in vitro by both prokaryotic and eukaryotic RNA polymerases is more efficient with negatively supercoiled DNA than with free DNA; presumably less free energy is required for the initial melting of DNA in the initiation complex.193
Role of Sperm DNA Damage in Male Infertility Assessment
Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh in Male Infertility in Reproductive Medicine, 2019
During spermiogenesis, the paternal genome undergoes precise packaging that imparts a unique architecture and compactness to the nucleus, which is crucial for fertilization and embryogenesis [4]. McPherson and Longo [21,22] proposed the indispensable role of endogenous nuclease, topoisomerase II, in chromatin packing. It is primarily involved in creating and ligating nicks that facilitates protamination. This drastic change in DNA topology provides relief of torsional stress and aids chromatin reorganization during the dislodgment of histones by protamines [4,21]. Topoisomerase II changes DNA topology by inducing double-strand break and its subsequent religation [23]. The unresolved strand breaks due to failure in the religation process by topoisomerase II can have adverse consequences on the genomic integrity of male gamete. Endogenous nicks in DNA are evident during the transition from round to elongated spermatids in the testis but not detected once the chromatin packing is complete [21,22]. Therefore, the presence of endogenous strand breaks in ejaculated spermatozoa signifies incomplete maturation during spermiogenesis.
The Use of Molecular Hybridization Techniques as Tools to Evaluate Hepatic Fibrogenesis
Marcos Rojkind in Connective Tissue in Health and Disease, 2017
During the past 2 decades, progress in our understanding of the basic principles of nucleic acid structure and interaction has made it possible to use recombinant DNA probes to study gene organization and function. Molecular hybridization is a reaction between two molecules of DNA or one molecule of DNA and RNA, based on the ability of complementary nucleotides in these molecules to interact and form stable base pairs by hydrogen bonding (adenine [A] recognizes thymidine [T] or uracil [U], and guanine [G] recognizes cytosine [C]). This bonding is the same principle which forms the basis of the Watson-Crick structure of DNA, the "double helix". Molecular hybridization can precisely quantitate the content of a specific mRNA sequence and is not dependent on an assay requiring biological activity. This represents an advantage over assays utilizing cell-free protein synthesis, since the latter may be highly variable and is not quantitative.21,22
Irinotecan hydrochloride trihydrate loaded folic acid-tailored solid lipid nanoparticles for targeting colorectal cancer: development, characterization, and in vitro cytotoxicity study using HT-29 cells
Published in Journal of Microencapsulation, 2019
Kuldeep Rajpoot, Sunil K. Jain
Irinotecan hydrochloride trihydrate (IHT), a water-soluble semisynthetic derivative of camptothecin, frequently used in the management of CRC and malignancies related to small cells in the lung (Bansal et al.2008, Maltas et al.2013). IHT is identified to interact precisely with the topoisomerase that regulates DNA topology and accomplish various nuclear processes, viz., DNA replication, recombination, and repair. IHT binds to the topoisomerase I and stop the replication of DNA (de Jong et al.2006). Current research reported that IHT is responsible for damage of double-strand of DNA during the interaction of replicating enzymes with ternary complex produced using DNA, topoisomerase I, and IHT. Thus, IHT prevents the synthesis of new DNA molecules needed for the mammalian cells by inhibiting the repairing of double-strand breaks in DNA (Charasson et al.2002). While in transcription, the IHT inactivates enzyme (forming a covalent complex, i.e. DNA and topoisomerase-I enzyme) to hinder RNA formation. Cytotoxicity of the IHT drug for S-phase is specific in the cell cycle (Morland et al.2014). In the case of CRC, the DNA replication in a tumour cell can be inhibited via the use of IHT (Tamyurek et al.2015).
Bacterial death from treatment with fluoroquinolones and other lethal stressors
Published in Expert Review of Anti-infective Therapy, 2021
Many bacterial species contain two type-II DNA topoisomerases, DNA gyrase and DNA topoisomerase IV (some, such as Mycobacterium tuberculosis, contain only gyrase). These enzymes alter DNA topology by introducing a double-strand break, passing another duplex (or a another region of the same duplex) through the break, and then resealing the break. The quinolones form complexes with either gyrase or topoisomerase IV and DNA that is broken such that each 5ʹ end is covalently bound to either GyrA (gyrase) or ParC (topoisomerase IV) [15,16]. Since the DNA is broken, the complex is called a cleaved complex (Figure 3). The presence of a covalent protein-DNA link allows the DNA break to readily reseal when quinolone is removed. As expected, cleaved-complex formation in vitro is reversible [17,18].
DNA topoisomerases as molecular targets for anticancer drugs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Kamila Buzun, Anna Bielawska, Krzysztof Bielawski, Agnieszka Gornowicz
DNA topoisomerases are a group of enzymes that control DNA topology. They are involved in many significant biological processes in all cells (e.g. DNA replication, transcription and recombination or chromosome condensation)6. These enzymes bind covalently to the DNA phosphorus group, split the DNA strand or strands and finally reunite them. According to their mechanism of action, there are two main types of topoisomerases: topoisomerases I (Top I) and topoisomerases II (Top II) divided into five subfamilies (see Table 1).
Related Knowledge Centers
- Adenine
- Cytosine
- DNA
- Nucleic Acid
- Nucleobase
- Nucleotide
- Phosphodiester Bond
- Rna
- Guanine
- Biomolecular Structure