瑞典乌普萨拉大学生命科学实验室Johan Elf和Sebastian Deindl课题组合作发现了DNA结合的序列特异性主要由关联决定。该项研究成果发表在2022年1月28日出版的《科学》上。

他们推导出了一个模型，该模型预测了 DNA 结合蛋白的宏观关联和解离率之间的反相关性。他们使用蛋白质结合微阵列并通过观察单分子实验中单个 lac 阻遏分子的动力学，测试了数千个不同 lac 操纵子序列的模型。他们发现序列特异性主要取决于蛋白质识别不同靶标的效率。识别不同靶标的概率变化至少是微观解离率变化的 1.7 倍。调节结合速率而不是解离速率可有效降低蛋白质在搜索时保留在非目标序列上的风险。

据介绍，蛋白质与 DNA 的序列特异性结合对于获取遗传信息至关重要。

附：英文原文

Title: Sequence specificity in DNA binding is mainly governed by association

Author: Emil Marklund, Guanzhong Mao, Jinwen Yuan, Spartak Zikrin, Eldar Abdurakhmanov, Sebastian Deindl, Johan Elf

Issue&Volume: 2022-01-28

Abstract: Sequence-specific binding of proteins to DNA is essential for accessing genetic information. We derive a model that predicts an anticorrelation between the macroscopic association and dissociation rates of DNA binding proteins. We tested the model for thousands of different lac operator sequences with a protein binding microarray and by observing kinetics for individual lac repressor molecules in single-molecule experiments. We found that sequence specificity is mainly governed by the efficiency with which the protein recognizes different targets. The variation in probability of recognizing different targets is at least 1.7 times as large as the variation in microscopic dissociation rates. Modulating the rate of binding instead of the rate of dissociation effectively reduces the risk of the protein being retained on nontarget sequences while searching.

DOI: abg7427

Source: https://www.science.org/doi/10.1126/science.abg7427