posted on 2021-02-11, 14:39authored byKe Lu, Cuifang Liu, Yinuo Liu, Anfeng Luo, Jun Chen, Zhichao Lei, Jingwei Kong, Xue Xiao, Shuming Zhang, Yi-Zhou Wang, Lu Ma, Shuo-Xing Dou, Peng-Ye Wang, Ming Li, Guohong Li, Wei Li, Ping Chen
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.