DNA Modifications

Salmonella typhimurium (reverse mutation) Escherichia coli (forward mutation, DNA modification) Saccharomyces cerevisia (reverse mutation) Bacillus subtilis (rec assay) Gene mutation or DNA modification Bruce and Heddle 1979 Dunkel et al. 1984 Fukunaga et al. 1982 Kharab and Singh 1985 Nestmann et al. 1979 Nishioka 1975 Rosenkranz and Poirier 1979 Simmon 1979b... 

Tests for gene mutations, DNA modifications, and recombinations in various microorganisms using lead acetate, lead nitrate, and lead chloride gave equivocal results (Bruce and Heddle 1979 Dunkel et al. 

Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed... 

Brabec, V. DNA Modifications by Antitumor Platinum and Ruthenium Compounds Their Recognition and Repair, Academic Press Amsterdam, 2002 Vol. 71 pp 2-45. 

The level of DNA modification in any biological system is low, ranging up to about one adduct per 105 bases in the DNA helix. Any methods used to detect such damage must therefore either be very sensitive or involve some method by which the effect of such damage is amplified to measurable levels. 

Thus, as more specific monoclonal antibodies are prepared, it should become possible to determine not only the total extent of DNA modification but also to gain insight into the structural and conformational properties of such modified DNA. 

The story of DNA replication is followed by one of DNA modification. The most important chemical modification of DNA is methylation that is, the methyl group, CH3—, is added to two of the bases of DNA, adenine (A) and cytosine (C). Three modified bases are formed. 

DNA modification of a commercial carbon ink without any electrochemical preconditioning by dry-adsorption was also reported. The surface was modified by covering with dsDNA solution and leaving the electrode to dry overnight. A stable, thin (about 100 p,m) DNA layer was obtained [111, 112]. The dsDNA was also demonstrated to be stably adsorbed when entrapped in a cellulose-acetate-based film on the surface of a carbon-based ink [113]. 

Nath RG, Li D, Randerath K. 1990. Acute and long-term effects of carbon tetrachloride on DNA modifications (l-compounds) in male mouse liver. Chem Biol Interactions 76 343-357. 

Following integration into the host genome as a provirus, the genome of a retrovirus is similar in many respects to a typical eucaryotic cellular gene. The transcription of the HIV coding DNA, modification and processing of the HIV transcript is performed by... 

Newbold, R.F., Warren, W., Medcalf, A.S.C. Amos, J. (1980) Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature, 283, 596-599... 

English, J.C., Hill, T., O Donoghue, J.L. Reddy, M.V. (1994b) Measurement of nuclear DNA modification by zp-postlabeling in the kidneys of male and female Fischer 344 rats after multiple gavage doses of hydroquinone. Fundam. appl. Toxicol., 23, 391-396... 

Davies, J.E., Mynett, K., Gescher, A. Chipman, J.K. (1993) DNA modification and repair by 2-nitropropane is extensive in hepatocytes of rats compared to those of humans and mice. Mutat. Res., I l, 157-164... 

In cases A, B and C, the DNA base or sugar modifications can be introduced via automated solid-phase synthetic methods using suitable DNA building blocks. As an alternative route, DNA modifications can be introduced by solid-phase methods which are applied during or after the complete automated solid-phase synthesis, as is the case for the preparation of the DNA assays B and D. 

Alternatively to the DNA modifications in the previous two sections where the chromophore was attached to one of the four DNA bases, chromophores can be incorporated as artificial DNA bases substituting a natural base or even a whole base-pair. There is a large number of recently reported syntheses of chromophores as DNA base surrogates, e.g. flavine derivatives [26] and thiazole orange derivatives [42]. Additionally, a variety of phosphoramidites as DNA building blocks for the introduction of fluorophores into DNA are commercially available, e.g. acridine derivatives. Clearly, the synthetic protocols for this kind of DNA modification do not follow a principle strategy which can be applied in a versatile fashion, as is the case for the DNA base modifications mentioned in the previous sections. It is important to point out that in many cases it turned out to be useful to replace the 2 -deoxyribose moiety with acyclic linker systems. This was also the case during our attempts to synthesize ethidium-modified DNA, which will be described here briefly. 

The challenge in this technology is to generalize this compartment approach to reactions other than DNA modification. The discrimination of DNA-bound product and DNA linked to educt will be an important step in this endeavor. 

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