Bromination stabilizes poly(dG-dC) in the Z-DNA form under low-salt conditions

Abstract

Using circular dichroism studies, Pohl & Jovin (1972) [Pohl, F.M., & Jovin, T.M. (1972) J. Mol. Biol. 67, 375-396] demonstrated that poly(dG-dC) undergoes a salt-dependent conformational change characterized by a spectral inversion. The low-salt form corresponds to the right-handed B form of DNA and the high-salt form to the left-handed Z-DNA helix. Modification of poly(dG-dC) by adding bromine atoms to the C8 position of guanine and the C5 position of cytosine residues stabilized this polymer in the Z-DNA form under low-salt conditions. The guanine residues were found to be twice as reactive as the cytosine residues. With a modification of 38% Br8G and 18% Br5C, the polymers formed a stable Z-DNA helix under physiological conditions. The bromination produced spectroscopic features very similar to poly(dG-dC) in 4 M NaCl. However, bromination did not freeze the Z structure as was shown by ethidium bromide intercalation studies. Addition of the dye favored an intercalated B-DNA form. The conversion of B- to Z-DNA leads to profound conformational changes which were also seen by a reduced insensitivity to various exo- and endonucleases. Comparative studies showed that the brominated polymers have a high affinity to nitrocellulose filters. In 1 M NaCl, there was virtually no binding of B-DNA, but a substantial binding of Z-DNA was found even at rather low levels of bromination.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors

“…BrdUrd, BrdC, and oxidants generated by white blood cells may contribute also to mutagenesis by creating an imbalance in the nucleotide pool (50,51). Moreover, bromination of cytosine has long been recognized to alter the secondary structure of DNA, favoring the formation of Z-DNA (52). Brominated pyrimidine compounds exhibit antiviral activity and alter normal nucleotide metabolism (53,54).…”

Interaction of RecA protein with acidic phospholipids inhibits DNA-binding activity of RecA

“…The DNAcontaining fractions were pooled, lyophilized, phenol-chloroform extracted, and then ethanol precipitated. Poly(dGdC) was converted to the left-handed Z-DNA conformation with 3.7 M NaCl and then stabilized in this conformation by bromination (32). The Z-DNA conformation of the polynucleotide was verified by UV absorption and CD spectroscopy (33).…”

31P-NMR analysis of the B to Z transition in double-stranded (dC-dG)3, and (dC-dG)4in high salt solution

“…Also, 31P NMR spectra of the left handed Z DNA of polynucleotides show two characteristic signals with separation or ca. 0.5-1.5 ppm, which can be used to detect the presence of Z DNA in solution (3,6,8,9,(15)(16)(17)(18)(19)(20)(21)(22)(23). It is usual to assume that the downfield and upfield components correspond to predominantly gt and gg conformations, respectively, of the i and a torsion angles (24) in the 03'-P-05' linkages (6,(15)(16)(17)(18)(19)(20)(21)(22)(23) …”