摘要：Modification of deoxyguanosine at the C8 position by the carcinogen N -acetoxy- N -2-acetylaminofluorene (N-AcO-AAF) has been shown to result in two different conformational changes dependent on the nucleotide sequence of the modified polymer. AAF modification of random sequence DNA results in a large distortion of the helix which is termed base displacement. In this conformation, the carcinogen is inserted into the DNA perpendicular to the helix axis with the guanosine displaced to the outside. Large single-stranded regions are generated which are susceptible to S1 nuclease digestion and react with anti-cytidine antibodies. A different conformation has been observed when the alternating purine pyrimidine copolymer, poly(dG-dC)·poly(dG-dC) is modified. At a modification level of 28% this polymer shows a CD spectrum characteristic of the left-handed Z-DNA seen in the unmodified polymer at high ethanol or salt concentrations. Base pairing of the modified polymer remains intact as demonstrated by its resistance to digestion with S1 nuclease and lack of reactivity with anti-cytidine antibodies. Modification of poly(dG-m5dC)·poly(dG-m5dC) with AAF was also shown to induce the Z conformation. However, for this polymer, inversion of the CD spectrum takes place at a much lower modification level (10%) than for the nonmethylated polymer (>20%). This polymer is also resistant to S1 nuclease digestion consistent with its adoption of the Z conformation with AAF modification. A possible role in gene expression for the Z conformation of AAF modified regions is discussed. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 107 108 109 110 111 112 113 114 115
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