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  • 标题:Sequence effects on local DNA topology.
  • 本地全文:下载
  • 作者:V P Chuprina ; A A Lipanov ; O Y Fedoroff
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1991
  • 卷号:88
  • 期号:20
  • 页码:9087-9091
  • DOI:10.1073/pnas.88.20.9087
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1' protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1' distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 A depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is greater than 4.5 A. In GA steps, x varies within rather wide limits in the range 3.8-4.5 A, whereas in AA steps the lower limit is 3.7 A and the upper limit is approximately 4.2 A. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5' end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3' end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3' end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B' structure when the substitution produces an AnTm tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1' distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1' distances depending on the DNA sequence. By using high-resolution x-ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1'-H1'. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs.
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