Liu Zhirong, Deibler Richard W, Chan Hue Sun, Zechiedrich Lynn
College of Chemistry and Molecular Engineering, and Center for Theoretical Biology, Peking University, Beijing 100871, China.
Nucleic Acids Res. 2009 Feb;37(3):661-71. doi: 10.1093/nar/gkp041.
The nucleotide sequence of DNA is the repository of hereditary information. Yet, it is now clear that the DNA itself plays an active role in regulating the ability of the cell to extract its information. Basic biological processes, including control of gene transcription, faithful DNA replication and segregation, maintenance of the genome and cellular differentiation are subject to the conformational and topological properties of DNA in addition to the regulation imparted by the sequence itself. How do these DNA features manifest such striking effects and how does the cell regulate them? In this review, we describe how misregulation of DNA topology can lead to cellular dysfunction. We then address how cells prevent these topological problems. We close with a discussion on recent theoretical advances indicating that the topological problems, themselves, can provide the cues necessary for their resolution by type-2 topoisomerases.
DNA的核苷酸序列是遗传信息的储存库。然而，现在很清楚的是，DNA本身在调节细胞提取其信息的能力方面发挥着积极作用。除了由序列本身赋予的调控外，包括基因转录控制、忠实的DNA复制和分离、基因组维护以及细胞分化在内的基本生物学过程还受到DNA的构象和拓扑性质的影响。这些DNA特征是如何产生如此显著的影响的，细胞又是如何对其进行调控的呢？在这篇综述中，我们描述了DNA拓扑结构的失调如何导致细胞功能障碍。然后我们探讨细胞如何预防这些拓扑问题。最后，我们讨论了最近的理论进展，这些进展表明拓扑问题本身可以为II型拓扑异构酶解决这些问题提供必要的线索。
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