Non-B DNA Secondary Structures and Their Resolution by RecQ Helicases.

Non-B DNA Secondary Structures and Their Resolution by RecQ Helicases.
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DOI:
10.4061/2011/724215
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发表时间:
2011
影响因子:
2.3
通讯作者:
Sharma S
Sharma S
中科院分区:
其他
文献类型:
--
作者:
Sharma S

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除了沃森和克里克首先描述的典型 B 型结构外,DNA 还可以采用许多替代结构。这些非 B 型 DNA 二级结构在基因组中大量的重复序列上自发形成。此外,具有链内配对的 DNA 的结构化形式可能出现在各种细胞过程中瞬时产生的单链 DNA 上。这种二级结构具有一系列生物学功能,但也会引起遗传不稳定。越来越多的证据表明,非 B DNA 二级结构引起的基因组不稳定性会导致疾病易感性。 DNA 二级结构也代表了 DNA 相互作用化合物的一类新的分子靶标,可能有助于靶向端粒和转录控制。双链 DNA 和多链非 B 型结构形成之间的平衡部分取决于解旋(解析)这些替代 DNA 结构的解旋酶。本文特别关注四链体、三链体和十字形,总结了非 B DNA 结构的发生率及其与基因组不稳定性的关联,并强调了 RecQ 样 DNA 解旋酶通过解析 DNA 二级结构在基因组维护中的作用。未来,RecQ 解旋酶预计将成为癌症化疗的额外分子靶点。
In addition to the canonical B-form structure first described by Watson and Crick, DNA can adopt a number of alternative structures. These non-B-form DNA secondary structures form spontaneously on tracts of repeat sequences that are abundant in genomes. In addition, structured forms of DNA with intrastrand pairing may arise on single-stranded DNA produced transiently during various cellular processes. Such secondary structures have a range of biological functions but also induce genetic instability. Increasing evidence suggests that genomic instabilities induced by non-B DNA secondary structures result in predisposition to diseases. Secondary DNA structures also represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres and transcriptional control. The equilibrium between the duplex DNA and formation of multistranded non-B-form structures is partly dependent upon the helicases that unwind (resolve) these alternate DNA structures. With special focus on tetraplex, triplex, and cruciform, this paper summarizes the incidence of non-B DNA structures and their association with genomic instability and emphasizes the roles of RecQ-like DNA helicases in genome maintenance by resolution of DNA secondary structures. In future, RecQ helicases are anticipated to be additional molecular targets for cancer chemotherapeutics.