Curaxin-Induced DNA Topology Alterations Trigger the Distinct Binding Response of CTCF and FACT at the Single-Molecule Level

文献类型： 外文期刊

第一作者： Lu, Ke

作者： Lu, Ke;Liu, Yinuo;Kong, Jingwei;Xiao, Xue;Zhang, Shuming;Ma, Lu;Dou, Shuo-Xing;Wang, Peng-Ye;Li, Ming;Li, Wei;Lu, Ke;Liu, Yinuo;Kong, Jingwei;Xiao, Xue;Zhang, Shuming;Ma, Lu;Dou, Shuo-Xing;Wang, Peng-Ye;Li, Ming;Li, Wei;Lu, Ke;Kong, Jingwei;Xiao, Xue;Dou, Shuo-Xing;Wang, Peng-Ye;Li, Ming;Li, Guohong;Liu, Cuifang;Li, Guohong;Chen, Ping;Luo, Anfeng;Chen, Jun;Chen, Ping;Lei, Zhichao;Lei, Zhichao;Zhang, Shuming;Zhang, Shuming;Wang, Yi-Zhou;Wang, Peng-Ye;Li, Ming;Li, Wei

作者机构：

期刊名称：BIOCHEMISTRY （ 影响因子：3.162； 五年影响因子：3.045 ）

ISSN： 0006-2960

年卷期： 2021 年 60 卷 7 期

页码：

收录情况： SCI

摘要： The candidate anticancer drug curaxins can insert into DNA base pairs and efficiently inhibit the growth of various cancers. However, how curaxins alter the genomic DNA structure and affect the DNA binding property of key proteins remains to be clarified. Here, we first showed that curaxin CBL0137 strongly stabilizes the interaction between the double strands of DNA and reduces DNA bending and twist rigidity simultaneously, by single-molecule magnetic tweezers. More importantly, we found that CBL0137 greatly impairs the binding of CTCF but facilitates trapping FACT on DNA. We revealed that CBL0137 clamps the DNA double helix that may induce a huge barrier for DNA unzipping during replication and transcription and causes the distinct binding response of CTCF and FACT on DNA. Our work provides a novel mechanical insight into CBL0137's anticancer mechanisms at the nucleic acid level.

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