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.
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.
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. This process prevents the accumulation of supercoiling and torsional stress that could otherwise lead to DNA damage and instability.
If this process doesn't occur, transcription can be hindered, leading to double-strand DNA breaks and genomic instability. This can cause the cell to die and trigger apoptosis.
[
Collection
]
[
|
...
]