Scientists have discovered how interactions between RNA and the TOP1 essential enzyme, which is overexpressed in many human cancers, regulate DNA during transcription and may inform the creation of new cancer therapies, according to a Northwestern Medicine study published in Molecular Cell . "This study offers new mechanistic insights that could pave the way for developing novel chemotherapeutics by targeting the RNA binding interface with small compounds. Our findings reveal that inhibiting RNA binding of TOP1 may work similarly to well-known TOP1 inhibitors like camptothecin by increasing TOP1 catalytic complexes on DNA.
"This approach could induce genomic instability and potentially enhance our ability to kill cancer cells," said Shannon Lauberth, Ph.D., associate professor of Biochemistry and Molecular Genetics and senior author of the study.
"By developing drugs that can precisely control the binding and release of RNAs bound by TOP1, we may enhance the efficacy of existing cancer therapies but also make significant strides toward the development of new therapeutics," said Kouki Abe, Ph.D., a postdoctoral fellow in the Lauberth laboratory and co-first author of the study.
Topoisomerase I (TOP1) is an enzyme known for its role in preventing genomic instability by alleviating torsional strain in DNA by introducing transient single-strand breaks. According to Lauberth, this process of DNA relaxation prevents the accumulation of supercoiling and torsional stress that could o.