Abstract
THE target sequence of the restriction enzyme NarI (GGCGCC) is a hot spot for the −2 frameshift mutagenesis (GGCGCC→GGCC) induced by the chemical carcinogens such as N-2-acetyl-aminofluorene1,2. Of the guanine residues, all of which show equal reactivity towards the carcinogen, only binding to the 3'-most proximal guanine within the Narl site is able to trigger the frameshift event3. We selected the non-palindromic dodecamer d(ACCGGCGCCACA), whose sequence corresponds to the most mutagenic Narl site in pBR322 DNA, for X-ray structure analysis. Its molecular structure determined at 2.8 å resolution reveals significant deviations from the structure of canonical B-form DNA, with partial opening of three G-C base pairs, high propeller twist values and sequence-dependent three-centred hydrogen bonds. This crystal structure shows a novel kind of packing in which helices are locked together by groove-backbone interactions. The partial opening of G-C base pairs is induced by interactions of phosphate anionic oxygen atoms with the amino group of cytosine bases. This provides a model for close approach of DNA molecules during biological processes, such as recombination.
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Timsit, Y., Westhof, E., Fuchs, R. et al. Unusual helical packing in crystals of DNA bearing a mutation hot spot. Nature 341, 459–462 (1989). https://doi.org/10.1038/341459a0
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DOI: https://doi.org/10.1038/341459a0
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