Unusual helical packing in crystals of DNA bearing a mutation hot spot

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-aminofluorene. Of the guanine residues, all of which show equal reactivity towards the carcinogen, only binding to the 3'-most proximal guanine within the NarI site is able to trigger the frameshift event. We selected the non-palindromic dodecamer d(ACCGGCGCCACA), whose sequence corresponds to the most mutagenic NarI site in pBR322 DNA; for X-ray structure analysis. Its molecular structure determined at 2.8 A 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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Contributor : Youri Timsit <>
Submitted on : Tuesday, February 5, 2019 - 4:00:02 PM
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R Timsit, Eric Westhof, Robert Fuchs, Dino Moras, Y. Timsit. Unusual helical packing in crystals of DNA bearing a mutation hot spot. Nature, Nature Publishing Group, 1989, 341 (6241), pp.459-462. ⟨10.1038/341459a0⟩. ⟨hal-02008266⟩



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