Fig. 5. Mechanism of curaxin action in cancer cells: N-trapping.

In the cells without curaxin treatment (−Curaxins), FACT loosely interacts with the transiently exposed DNA binding surface of the H2A/H2B dimer and thus facilitates transcription through the nucleosome barrier. In the presence of curaxins (+Curaxins), FACT causes genome-wide nucleosome unfolding and is tightly trapped on the unfolded nucleosomes (n-trapping). Because the nontranscribed chromatin is present in vast excess, FACT is trapped primarily within inactive chromatin regions. Thus, curaxin-induced n-trapping reduces density of FACT on transcribed regions, resulting in loss of FACT from the transcribed genes and likely affects chromatin dynamics and/or transcript elongation process.