期刊
NUCLEIC ACIDS RESEARCH
卷 48, 期 4, 页码 1748-1763出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz1227
关键词
-
资金
- Engineering and Physical Sciences Research Council (EPSRC) [1506874, EP/N027639/1]
- Biology and Biotechnology Research Council (BBSRC) [BB/R001235/1]
- Leverhulme Trust [RPG-2017-340]
- Royal Academy of Engineering [LTSRF1617/13/58]
- University of York
- BBSRC [BB/N006453/1, BB/R001235/1] Funding Source: UKRI
- EPSRC [EP/N027639/1, EP/L000253/1] Funding Source: UKRI
The double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations resulting from mechanical perturbations in cells have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations showing sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulate overextension on different sequences of DNA ((AA)(12), (AT)(12), (CC)(12) and (CG)(12)) with supercoiling densities at 200 and 50 mM salt concentrations. We find that DNA denatures in the majority of stretching simulations, surprisingly including those with over-twisted DNA. GC-rich sequences are observed to be more stable than AT-rich ones, with the specific response dependent on the base pair order. Furthermore, we find that (AT)(12) forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (CG)(12) forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20-30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据