Cloutier T E, Widom J
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3645-50. doi: 10.1073/pnas.0409059102. Epub 2005 Feb 17.
Gene-regulatory complexes often require that pairs of DNA-bound proteins interact by looping-out short (often approximately 100-bp) stretches of DNA. The loops can vary in detailed length and sequence and, thus, in total helical twist, which radically alters their geometry. How this variability is accommodated structurally is not known. Here we show that the inherent twistability of 89- to 105-bp DNA circles exceeds theoretical expectation by up to 400-fold. These results can be explained only by greatly enhanced DNA flexibility, not by permanent bends. They invalidate the use of classic theories of flexibility for understanding sharp DNA looping but support predictions of two recent theories. Our findings imply an active role for DNA flexibility in loop formation and suggest that variability in the detailed helical twist of regulatory loops is accommodated naturally by the inherent twistability of the DNA.
基因调控复合物通常要求成对的与DNA结合的蛋白质通过使短的(通常约100个碱基对)DNA片段成环来相互作用。这些环在详细的长度和序列上会有所不同,因此在总的螺旋扭转方面也会不同,这会从根本上改变它们的几何形状。目前尚不清楚这种变异性在结构上是如何被容纳的。在这里,我们表明89至105个碱基对的DNA环的固有可扭转性比理论预期高出多达400倍。这些结果只能通过大大增强的DNA灵活性来解释,而不是通过永久性弯曲来解释。它们使利用经典的灵活性理论来理解尖锐的DNA成环变得无效,但支持了最近两个理论的预测。我们的发现暗示了DNA灵活性在环形成中发挥着积极作用,并表明调控环详细螺旋扭转的变异性通过DNA的固有可扭转性自然地得到了容纳。