In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).
Structural parameters characterizing the bending propensity of trinucleotides were deduced from DNase I digestion data using simple probabilistic models. In contrast to dinucleotide‐based models of DNA bending and/or bendability, the trinucleotide parameters are in good agreement with X‐ray crystallographic data on bent DNA. This improvement may be due to the fact that the trinucleotide model incorporates more sequence context information than do dinucleotide‐based descriptions.
The repetitive sequence (AGGGCCCTAGAGGGGCCC-TAG)n was previously shown to be curved by gel mobility assays. Here we show, using hydroxy radical/DNase I digestion and differential helical phasing experiments that the curvature is directed towards the major groove and is located in the GGGCCC, but not the CTAGAG segments. The effect of the GC step in the context of the GGGCCC motif is apparently about as large as that of AA/TT, i.e. enough to cancel the macroscopic curvature of helically phased A-tracts. These data are in agreement with positive roll-like curvature of the GCC/GGC motif, predicted from nucleosome packing data and the 3D structure of the GGGGCCCC octamer, but they are not in agreement with the dinucleotide-based roll angle values predicted for AG/CT, TA, GG/CC and GC steps. Our results thus indicate the importance of interactions beyond the dinucleotide steps in predictive models of DNA curvature.
DNaseI digestion studies (Brukner et al, EMBO J 14, 1812-1818 1995) and nucleosomebinding data (Satchwell et al, J. Mol. Biol. 191, 639-659 1986, Goodsell and Dickerson, Nucleic trinucleotides. A detailed comparison of the two models suggests that while both of them represent improvements with respect to dinucleotide based descriptions, the individual trinucleotide parameters are not highly correlated (linear correlation coefficient is 0.53), and a number of motifs such as TA-elements and CCA/TGG motifs are more realistically described in the DNaseI-based model. This may be due to the fact that the DNaseI-based model does not rely on a static geometry but rather captures a dynamic ability of ds DNA to bend towards the major grove. Future refinement of both models of both models on larger experimental data sets is expected to further improve the prediction of macroscopic DNA-curvature.
Two global helix parameters important for DNA-DNase I interaction are the geometry of the minor groove and the DNA stiffness that resists bending toward major groove. Thus, local averaging of P-O3' bonds cutting frequencies (InP) reflects global helix parameters revealed by DNase I. Using the approximation that locally averaged InP values depend only on the type of the dinucleotide steps involved in the region of interaction, we calculated the collective contribution (sigma Dd) for ten different dinucleotide steps. Our results suggest that, at the first approximation, global varying helix parameters revealed by DNase I, might be predicted from sequence. Obtained sigma Dd function can be used as a sequence-dependent measure of protein-induced DNA flexure in the direction towards the major groove, which is usually connected to widening of the minor groove. In the course of analysis of Mg2+ and Mn2+ dependent DNase I digestions, no significant difference was found, in spite of the supposed differences in enzyme activity. These results suggest that if the second Mn2(+)-dependent active site exists, its activity is lower than that of the first one.
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