The heat shock transcription factor, HSF1, facilitates the catalytic engagement of topoisomerase IIb (TOP2B) within the neuronal genome

Using atomic force microscopy, we show that HSF1 also enhances the recycling of TOP2B for subsequent rounds of DNA relaxation. TOP2B co-occupies the genome with HSF1 in both postmitotic and dividing cells, and either the knockdown or inhibition of HSF1 reduces the levels of catalytically engaged TOP2B. Intriguingly, HSF1 neither significantly interacts with TOP2A nor enhances its catalytic activity.

Furthermore, pharmacological HSF1 inhibitors protect postmitotic cells from the cytotoxicity of TOP2 poisons without compromising their ability to kill cancer cells, revealing a potential strategy for minimizing the side-effects of TOP2 poison-based chemotherapy.