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DNAase I hypersensitive sites may be correlated with genomic regions of large structural variation
Authors:R Nussinov  B Shapiro  L E Lipkin  J V Maizel
Institution:1. Laboratory of Molecular Genetics National Institute of Child Health and Human Development National Institutes of Health, Bethesda, MD 20205, U.S.A.;2. Laboratory of Mathematical Biology, Image Processing Section National Cancer Institute, National Institutes of Health Bethesda, MD 20205, U.S.A.
Abstract:Helical-twist, roll and torsion-angle variations calculated by the Calladine (1982)-Dickerson (1983) rules were scanned along several nucleotide sequences for which DNAase I cleavage data are available. It has been shown that for short synthetic oligomers DNAase I cuts preferentially at positions of high helical twist (Dickerson & Drew, 1981; Lomonossoff et al., 1981). Our calculations indicate that DNAase I sensitive and hypersensitive sites in chromatin are correlated with regions of successive, large, helical-twist angle variations from regular B-DNA. In many cases these regions exhibit large variations in base-pair roll and backbone torsion angles as well. It has been suggested that DNAase I cuts in the vicinity of cruciforms. However, it was recently demonstrated by Courey & Wang (1983) and Gellert et al. (1983) that such cruciform formation in a negatively supercoiled DNA is kinetically forbidden under physiological conditions. We thus propose that clustering of large twist-angle (and/or roll and backbone torsion angle) variations may be among the conformational features recognized by the enzyme. Specific cuts can then preferentially occur at base-pair steps with high helical twists.
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