Ultra-violet light induced changes in DNA dynamics may enhance TT-dimer recognition
Ultra-violet light induced changes in DNA dynamics may enhance TT-dimer recognition
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DOI：
10.1016/j.dnarep.2006.04.007
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发表时间：
2006-07-13
期刊：
影响因子：
3.8
通讯作者：
Bishop, A. R.
中科院分区：
文献类型：
--
作者：
Blagoev, K. B.;Alexandrov, B. S.;Bishop, A. R.
短波紫外线会促进相邻胸腺嘧啶碱基之间 DNA 二聚体的形成，如果不修复这些二聚体可能会诱发皮肤癌。活细胞具有非常强大的修复系统，每天能够修复数百个病变。尽管二聚体修复机制的许多细节是已知的，但二聚体是如何被识别的仍然是个谜。由于二聚体对细胞核中扩散的修复蛋白是隐藏的，因此推测二聚体识别是间接的。在本文中，双链 DNA 分子中两条链的运动中二聚体诱导的大幅度、长时间振荡的理论提出了一种新的识别信号。位于二聚体周围的两条 DNA 链的大幅振荡将揭示二聚体，从而使修复蛋白能够与二聚体位点结合。根据本文的研究结果，识别率的温度依赖性与链间波动相关，并且必须随着温度的降低而降低。此外，发现大开口的概率局限于二聚体附近，这些大开口可能在二聚体修复蛋白质生物化学中发挥重要作用。 (c) 2006 Elsevier B.V. 保留所有权利。
Short-wave ultra-violet light promotes the formation of DNA dimers between adjacent thymine bases, and if unrepaired these dimers may induce skin cancer. Living cells have a very robust repair system capable of repairing hundreds of lesions every day. Although many of the details of the dimer repair mechanism are known, it is still a mystery how the dimers are recognized. Because the dimers are hidden from repair proteins diffusing in the cell nucleus, it has been surmised that dimer recognition is indirect. In this paper, a new recognition signal is suggested by a theory of the dimer-induced large amplitude, prolonged oscillations in the motion of the two strands in double-stranded DNA molecules. These large amplitude oscillations of the two DNA strands, localized around the dimer will unveil the dimer allowing the repair proteins to bind to the dimer site. The temperature dependence of the recognition rate is correlated with the inter-strand fluctuations and must decrease with decreasing temperature according to the findings in this paper. Moreover the probability for finding a large opening is localized to the dimer neighbourhood and these large openings may play an important role in dimer-repair protein biochemistry. (c) 2006 Elsevier B.V. All rights reserved.