Friday, December 8, 2006

Statistical dynamics of DNA unzipping and RNA polymerase

今天的 Theory Lunch 請到 Harvard Physics & Biophysics 的 David Nelson,講有關 DNA unzipping 跟 RNA polymerase 解開 DNA double helix 的研究。我很喜歡今天的 talk,事實上這是少數幾場在以結束前完全沒有人離席的 talk,David 本身的幽默應該有幫助,另外一部分的原因是這邊的人比較能夠接受他這種類型的實驗方法。

David 主要的研究內容在用測量解開 DNA helix 所需要的力量,基本上就是從實驗這邊往理論方向作,由實驗數據反推隱藏在其後的理論,而不是先把理論模型弄好再跑數據看哪個符合。David 發現要解開 DNA helix 的力量的臨界質為 14.2 pN,任何低於此值的力道都無法穩定地打開雙股螺旋。之後依照此值改變溫度畫出 curve 再演算可能的 formula。David 依照這些結果,證明了在序列可造成影響的臨界質在哪裡,以及 autonomous mutation 的容忍度有多大,為甚麼突變或說不同的序列對於基因轉錄或 DNA 複製的影響不大。

簡單說,David 看起來像是蠻好的老師,用的技術主要還是物理方法,比如說用 optical tweezers 測量拉力,但他的想法跟策略我覺得是比較貼近我們這裡的幾個大頭,所以才沒有發生被痛電的情況。不過很明顯地他做的東西比較實際,不會像以往有些 talk 太形而上了。


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Statistical dynamics of DNA unzipping and RNA polymerase
8 December 2006

David Nelson
Lyman Laboratory of Physics
Harvard University

Abstract
The denaturation of double-stranded DNA as a function of force and temperature is discussed. At room temperature, sequence heterogeneity dominates the physics of single molecule force-extension curves starting about 7 pN below a ~15 pN unzipping transition. The dynamics of the unzipping fork exhibits anomalous drift and diffusion in a similar range above this transition. Energy barriers near the transition scale as the square root of the genome size. We will argue that similar ideas apply to the effect of sequence heterogeneity on molecular motors such as RNA polymerase near the stall force. Instead of simple diffusion with drift, the dynamics is characterized by sequence-dependent jumps and pauses, and the long time displacement grows sublinearly with time, as tμ with μ < 1. The resulting motor velocity is no longer well defined, but depends instead on the time scale of observation.

References
D R Nelson, "Statistical Physics of Unzipping DNA", arxiv.org/abs/cond-mat/0309559

Y Kafri, D K Lubensky, D R Nelson, "Dynamics of molecular motors and polymer translocation with sequence heterogeneity", Biophys J 86:3373-91 2004. PubMed

Y Kafri, D R Nelson, "Sequence heterogeneity and the dynamics of molecular motors", J Phys: Condens Matter, 17:S3871-86 2005. arxiv.org/abs/cond-mat/0506797
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演講時寫的白板內容(點圖可以放大)


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