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Molecular Biology and Gene Therapy
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Transcription is the intra-nuclear process driven by the RNA polymerase whereby one DNA strand acts as a template for the synthesis of an RNA strand (uracil replaces thymine in RNA). This primary RNA transcript then undergoes post-transcriptional processing, or splicing. The mature mRNA migrates into the cytoplasm where it acts as a template for the synthesis of a polypeptide during translation, via ribosomes. Successive amino acids are added creating a polypeptide chain from to the triplet code on the mRNA, resulting in protein synthesis.
Lifestyle Factors in Cancer Survivorship
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Dietary chemicals such as polycyclic aromatic hydrocarbons and aromatic amines, found in super-heated processed or fried foods, are converted to products that can directly or indirectly oxidize water or oxygen into short-lived, highly energetic free radicals. These can cause double or single DNA strand breaks, allowing cancer promoting genes to escape from the influence of their suppressor gene guardians. Numerous environmental studies have linked carcinogens to cancers, and the U.S. Food and Drug Agency (FDA) regularly publishes lists of foods and environmental chemicals such as pesticides, toxic additives, and chemical contaminants that are potentially carcinogenic if taken in sufficient quantities.
Our Radiation Environment
Published in T. D. Luckey, Radiation Hormesis, 2020
Many radiologists are overly concerned with direct “hits” on DNA or other macromolecules with little attention given to free radical formation. Particulate rays and photons disrupt DNA molecules by direct “hits”. The DNA in most cells has two complimentary strands bound together by thousands of hydrogen bonds. A break in one strand is usually repaired using the other strand as a template. This provides great precision in the duplication of the broken strand. However, germ cells have only one strand of DNA in the nucleus; they are haploid, not diploid. A break in one strand of a haploid cell or a simultaneous break in the same area of both strands in a diploid cell leaves no intact template for repair. The disrupted DNA strand either terminates the cell or provides the cell with a chromosomal aberration. Since only about 10% of the DNA is functional, the production of chromosomal aberrations may or may not be of biologic importance.733,734 A deranged chromosome may occasionally initiate mutation or cancer.
Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mohamed M. Khalifa, Ahmed A. Al-Karmalawy, Eslam B. Elkaeed, Mohamed S. Nafie, Mohamed A. Tantawy, Ibrahim H. Eissa, Hazem A. Mahdy
The current search and discovery of new drug candidates with anticancer activities have become one of the most important issues for medicinal chemists nowadays6–11. Among the most important chemotherapeutic agents applied for cancer treatment are those that interact with DNA. Anticancer agents in the previously mentioned class belong to either alkylating agents, groove binders, or intercalating agents12. DNA intercalating agents got great attention from scientists due to their promising antitumoral activity13–18. They are classified into two major groups of compounds that intercalate between DNA base pairs (especially G and C, 70%) without covalent binding: 1) acridines and related compounds and 2) anthracyclines and related compounds19. These compounds produce local structural changes to the DNA molecule, including the lengthening of the DNA strand following the unwinding of its double helix. So, DNA intercalators are mutagenic due to their retardation or even inhibition of DNA transcription and replication20.
Methanol extracts of Teucrium arduini L. and Teucrium flavum L. induce protective effect against mitomycin C in human lymphocytes in vitro
Published in Drug and Chemical Toxicology, 2022
Aleksandra Marković, Jovana Tubić Vukajlović, Darko Grujičić, Marina Radović Jakovljević, Milan Stanković, Katarina Djordjević, Ninoslav Djelić, Milena Radaković, Olivera Milošević-Djordjević
The studies have shown that in addition to the beneficial effects, plants extracts can cause toxic and mutagenic effects, which may be related to the concentration used and the length of treatment (Celik 2012, Al-Dulaimi et al.2017). The assays that evaluate genotoxicity and mutagenicity are fundamental for safety and efficacy assessment of medicinal plants. One of the most used is the CBMN assay in PBLs. This assay is widely used for its being simple, reliable, sensitive, inexpensive, and applicable to both in vivo and in vitro approaches (Araldi et al.2015). The micronuclei are arised from chromosome fragments as a result of chromosome breaks (double-stranded DNA breaks) or whole chromosome. On the other hand, the NDI is used as a biomarker of cell proliferation in cultures and is considered a measure of general cytotoxicity (Fenech 2000). In addition to the CBMN assay, the comet assay was commonly used in toxicological studies. This is a sensitive method for DNA damage estimation and provides direct determination of single DNA strand breaks in individual cells (Etebari et al.2012).
Emergence of varicella-zoster virus resistance to acyclovir: epidemiology, prevention, and treatment
Published in Expert Review of Anti-infective Therapy, 2021
Kimiyasu Shiraki, Masaya Takemoto, Tohru Daikoku
Double-stranded DNA needs to be separated into two single strands (replication fork) before DNA synthesis, and complementary strands are synthesized from each DNA strand to produce two new double-stranded DNA molecules during DNA replication (Figure 3). The HP complex is responsible for unwinding viral DNA at the replication fork, separating double-stranded DNA into two single strands, and synthesizing RNA primers (Okazaki fragments) in the lagging strand for DNA synthesis. DNApol initiates complementary DNA synthesis in the two separated DNA strands. The HP complex consists of three proteins: VZVORF55 (helicase), VZVORF6 (primase), and VZVORF52 (cofactor). The helicase unwinds the duplex DNA ahead of the fork and separates the double strand into two single strands. The primase lays down RNA primers that extend the two-subunit DNApol. The HP complex possesses multienzymatic activities, including DNA-dependent ATPase, helicase, and primase activities, all of which are required for the HP complex to function in viral DNA replication.