Effect on DNA

Mechanism of Action. THie earliest studies on the mechanism of action of lincomycin showed that lincomycin had the immediate effect on Staphjlococcus aureus of complete inhibition of protein synthesis (23). TThis inhibition results from the blocking of the peptidyltransferase site of the SOS subunit of the bacterial ribosome (24). Litde effect on DNA and RNA synthesis was observed. 

FIGURE 12.16 The structures of ethidiutn bromide, acridine orange, and actinomycin D, three intercalating agents, and their effects on DNA structure. 

Malek A, Czubayko F, Aigner A (2008) PEG grafting of polyethylenimine (PEI) exerts different effects on DNA transfection and siRNA-induced gene targeting efficacy. J Drug Target 16 124-139... 

P. Pellack-Walker, J. K. Walker, H. H. Evans, J. L. Blumer, Relationship between the Oxidation Potential of Benzene Metabolites and Their Inhibitory Effect on DNA Synthesis in L5178YS Cells , Mol. Pharmacol. 1985, 28, 560 - 566. 

Gregoriadis G, Saffle R, Hart SL. High yield incorporation of plasmid DNA within liposomes effect on DNA integrity and transfection efficiency. J Drug Target 1996 3 469 75. 

In the absence of crystallographic data, there exist many other experimental criteria that allow the determination of the binding mode [30,38]. They can be classified into two categories the measurement of physical effects on DNA and spectroscopic studies (Table 1, first column, C and A respectively). Irrespective of the binding mode, the binding parameters (the affinity constant and the number n of occupied base pairs per molecule) can be determined from equilibrium dialysis and Scatchard plots [43 46]... 

Crothers, D.M. (1993) Architectural elements in nucleoprotein structures. Curr. Biol. 3, 675-676. Stros, M. (2001) Two mutations of basic residues within the N-terminus of HMG-1 B domain with different effects on DNA supercoiling and binding to bent DNA. Biochemistry 40, 4769-4779. 

P34 During the study, it was discovered that Cr + causes DNA damage, has influence on DNA topology, most probably via effects on DNA gyrase, and also reduces the proliferation rate of certain eukaryotic cells. (From Plaper et ah, 2002)... 

Plaper, A. Jenko-Brinovec, S. Premzl, A. Kos, J. Raspor, P. Genotoxicity of Trivalent Chromium in Bacterial Cells. Possible Effects on DNA Topology. Chem. Res. Toxicol. 2002,15, 943-949. 

The biologic action of gemcitabine on its own is due almost completely to its effects on DNA metabolism. Early studies of this drug in leukemic cell lines showed that notable decreases in cellular dNTPs occurred with the use of the drug (8). These decreases were most impressive in terms of the levels of 2 -deoxycytidine 5 -triphosphate (dCTP), however, 2 -deoxyadenosine 5 -triphosphate (dATP) and 2 -deoxyguanosine 5 -triphosphate (dGTP) were also affected. It is felt that part of this is due to the inhibitory effects of... 

Mechanism of Action An antibacterial agent that inhibits bacterial protein, RNA synthesis. Less effective on DNA synthesis. Nasal Eradicates nasal colonization of MRSA. Therapeutic Effect Prevents bacterial growth and replication. Bacteriostatic. Pharmacokinetics Metabolized in skin to inactive metabolite. Transported to skin surface removed by normal skin desquamation. 

Wang C, Kurzer MS. Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr. Cancer 28, 236-247, 1997. 

There are many examples for the specific phosphorylation of gene regulating proteins within their DNA-binding domain. Phosphorylation can influence either positively or negatively the abiltiy to specifically bind DNA. The situation becomes comphcated by the fact that many transcriptional activators possess multiple phosphorylation sites, whose phosphorylation can have different effects on DNA-binding. 

The p53 protein has various Ser/Thr phosphorylation sites. These include C-terminal phosphorylation sites for the CDKs of the S and G2/M phase. A controlling effect on DNA binding ability has been described for C-terminal phosphorylation so that a direct connection between the cell cycle machinery and the transcription-activating function of p53 seems possible via this route. 

Under a variety of conditions, plasmid DNA undergoes a dramatic compaction in the presence of condensing agents such as multivalent cations and cationic polymers. Naked DNA coils, typically with a hydrodynamic size of hundreds of nanometers, after condensation it may become only tens of nanometer in size. Contrary to proteins which show a unique tertiary structure, DNA coils do not condense into unique compact structure. Cationic polymers execute their gene carrier function by their condensation effect on gene materials and, furthermore, their protection effect on DNA from nuclease digestion. Currently, the most widely used cationic polymers in research include linear or branched PEI (poly (ethyleneimine) (161-165), polypeptides such as PLL (poly-L-lysine) (166-169), PLA (poly-L-arginine) (170). 

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