Blagoev K B, Alexandrov B S, Goodwin E H, Bishop A R
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA.
DNA Repair (Amst). 2006 Jul 13;5(7):863-7. doi: 10.1016/j.dnarep.2006.04.007. Epub 2006 Jun 13.
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.
短波紫外线会促使相邻胸腺嘧啶碱基之间形成DNA二聚体，如果这些二聚体未得到修复，可能会诱发皮肤癌。活细胞拥有非常强大的修复系统，每天能够修复数百个损伤。尽管二聚体修复机制的许多细节已为人所知，但二聚体是如何被识别的仍然是个谜。由于二聚体对于在细胞核中扩散的修复蛋白来说是隐藏的，因此据推测二聚体识别是间接的。在本文中，双链DNA分子中两条链运动的二聚体诱导的大幅度、长时间振荡理论提出了一种新的识别信号。这两条DNA链围绕二聚体的大幅度振荡将揭示二聚体，使修复蛋白能够结合到二聚体位点。根据本文的研究结果，识别速率的温度依赖性与链间波动相关，并且必然会随着温度降低而降低。此外，出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生物化学中发挥重要作用。
