DNA Sequencing Method Explores Life-Saving Drugs

Many life-saving drugs interact directly with DNA to treat diseases like cancer, but scientists have struggled to understand how and why they work – until now. In a paper, researchers described a new DNA sequencing method to detect where and how small molecule drugs interact with the targeted genome.

Understanding how drugs work in the body is critical for developing more effective therapies. When a therapeutic drug enters a cancer cell with a three billion base genome, it’s like entering a black box. Chem-map is a powerful method that allows researchers to detect where small molecule drugs interact with their targets on the DNA genome, lifting the lid on this genomic black box.

Chem-map enables researchers to map small molecule-genome interactions in situ with unprecedented precision, thanks to a technique known as small-molecule-directed transposase Tn5 tagmentation. It identifies the genomic binding site where a small molecule binds to genomic DNA or DNA-associated proteins.

The researchers used Chem-map to identify the direct binding sites of the widely used anticancer drug doxorubicin in human leukemia cells. The technique also demonstrated how combining doxorubicin with the histone deacetylase (HDAC) inhibitor tucidinostat could have a potential clinical advantage.

The new DNA sequencing method was also used to map the binding sites of specific molecules on DNA G-quadruplexes, or G4s. G4s are four-stranded secondary structures linked to gene regulation and could be future anticancer targets.

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