Conformational Changes in Nucleic Acids Modified by Chemical Carcinogens
Philip L. Grover in Chemical Carcinogens and DNA, 2019
Although there has been a tendency to think of the DNA helix as a rigid rod-like structure, it is apparent that in the packaging of DNA that occurs in viruses and in cellular chromatin, the double helix must be folded into a higher order structure and that this folding must be associated with either a continuous or discontinuous deformation of the backbone structure of a Watson-Crick helix. The latter distortions have been termed “Kinks” by Crick and Klug,11 and their possible existence and structure is an active area of current research. Sobel et al.12 have postulated that kinks produced by bending a linear helix laterally, so as to open up a wedge-like space in the minor groove, may provide the initial sites for insertion of intercalating drugs, for the binding of certain DNA-associated proteins, and for the unwinding of the helix during denaturation and strand separation.
Topoisomerase II Inhibition by Antitumor Intercalators and Demethylepipodophyllotoxins
Robert I. Glazer in Developments in Cancer Chemotherapy, 2019
Chromatin organization has been described in recent reviews.10,11 The double-stranded DNA helix is wrapped around nucleosomes (approximately 150 bp and 1.5 superhelical turns). Linker regions between nucleosomes (50 to 100 bp) are bound to H1 histone. Nucleosome-DNA complexes form solenoid structures (30-nm diameter fibers) which are organized into chromatin loops (Figure 2). Loop size varies between 20 ~ 100 kbp and is determined by the attachment of the extremities of the loop to the chromosome scaffold (nuclear matrix attachment points). There is good evidence that topo II is bound at these attachment sites, since topo II has been identified as the previously described scaffolding protein, SC1.12 Both SC1 and topo II have similar molecular weights (170 kDa) and im-munoreactivities. In addition, SC1 antibodies block topo II function.13
Selective Gene De-Repression By De-Repressor RNA
M. Gerald, M.D. Kolodny in Eukaryotic Gene Regulation, 2018
The DNA helix must open in localized areas before the interior base-coded genetic information can be used for new RNA or DNA synthesis.31,37,38 These DNA helix openings can be visualized by a high-resolution electron microscopic technique24,39 which has been applied to individual cells undergoing normal cell division and differentiation,40 embryogenesis,41 and neoplasia.42,43 These DNA helix openings are sensitive to digestion with pancreatic DNase I18,24 which is relatively specific for single-strand cuts in DNA.44 Such DNA helix openings are found exclusively within transcription-active euchromatin,24 and range in size from 25 to 700 nm in length, corresponding to 70 to 2000 base pairs in DNA helix length.25
A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Robert Czarnomysy, Arkadiusz Surażyński, Anna Muszynska, Agnieszka Gornowicz, Anna Bielawska, Krzysztof Bielawski
Pinato et al. previously demonstrated that the pro-apoptotic activity of platinum compounds is associated with the production of DNA strand breaks42. Moreover, it is believed that pyrazole moiety damages the DNA strand, affecting the regulation of gene expression and epigenetic signaling pathways in tumors and numerous other diseases43. PtPz1–PtPz6 produced more extensive DNA fragmentation than cisplatin. This degradation represents the double strand breaks when the DNA helix existed in a double stranded form. Previous studies showed that pyrazoles have anti-tumor activity on different types of cancer cells: non-small cell lung cancer, human hormone-independent prostate cancer, stomach cancer, myeloid leukemia, sarcoma, gastric cancer, and cervical carcinoma44. Therefore, it is possible that pyrazole-platinum(II) complexes may be an effective scaffold for further research on complexes with potential anti-tumor activity.
DNA binding, BSA interaction and in-vitro antimicrobial studies of Cu(II), Co(III), Ni(II) and VO(IV) complexes with a new Schiff base
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Disha Sharma, Hosakere D. Revanasiddappa, Basavegowda Jayalakshmi
The interaction between the metal complexes and DNA was further confirmed by viscometric measurements. Although spectroscopic methods provide important evidence to support the mode of binding of metal complexes to DNA, hydrodynamic measurements are considered to be the best binding interaction of DNA in solution, without a crystallographic data [31,32]. Upon interaction of metal complex with DNA, this results in lengthening of its helix and can also accommodate ligand with increasing in viscosity. If partial binding of ligand leads to kink or bend of DNA helix with decrease in DNA length along with decrease in viscosity, a remarkable increase in DNA viscosity indicates intercalation mode of interaction of complex with DNA. This change has been observed in Figure 13. The results obtained from spectroscopic studies are in agreement with this result.
Insights and controversies on sunscreen safety
Published in Critical Reviews in Toxicology, 2020
Juliana P. Paiva, Raiane R. Diniz, Alvaro C. Leitão, Lucio M. Cabral, Rodrigo S. Fortunato, Bianca A. M. C. Santos, Marcelo de Pádula
The most frequent DNA lesions generated directly by UV radiation are the pyrimidine cyclobutane dimmers (CPDs) and the 6-4-pyrimidine-pyrimidone photoproducts (6-4PPs). These lesions are responsible for promoting structural alterations to the DNA helix, which can lead to the inhibition of replication and transcription. CPDs are formed after a covalent bond between two adjacent pyrimidine bases generating a cyclobutane ring formed from the saturation of the double bond between carbons 5 and 6 of the neighbor pyrimidine nitrogen bases (Friedberg et al. 2006). These bonds have a high mutagenic potential and need to be corrected by DNA repair mechanisms (Mancebo et al. 2014). The 6-4PPs are characterized by a covalent bond between the 5′ end of carbon 6 from a base to the 3′ end of carbon 4 from its adjacent base (Friedberg et al. 2006). These two lesions appear to induce differential biological effects in the cell exposed to UV. Scientific evidence suggests that 6-4PPs participate more effectively in UV-induced apoptosis, whereas CPDs appear to be more important in arresting progression cell cycle (Lo et al. 2005). The conversion of 6-4PPs into their Dewar valence isomers, other type of lesion, results from the intramolecular electrocyclization of the pyrimidone ring after the photon absorption (Perdiz et al. 2000; Douki 2016). The formation of a Dewar isomer requires at least two photons: the first induces the 6-4PP and the second, arisen from UVA, is required for the isomerization of the initial 6-4PP.
Related Knowledge Centers
- Biopolymer
- DNA
- Molecular Biology
- Nucleic Acid
- Nucleotide
- Base Pair
- Nucleic Acid Secondary Structure
- Nucleic Acid Tertiary Structure
- Triple-Stranded DNA
- Complementarity