Visualization of chromatin disassembly ongoing in tumor cell treated with an anticancer drug candidate curaxin CBL0137. Binding of CBL0137, as well as some other small molecules, to cellular DNA alters DNA helical structure, leading to nucleosome disassembly and loss of histones from chromatin. This is manifested as a shift from sharp to diffuse distribution of H1 histone tagged with mCherry fluorescent protein from the right to the left panel in the top row. This process is dependent on whether small molecules cause or do not cause DNA damage. Histone chaperone FACT binds destabilized nucleosomes in which a shift of the green fluorescence is seen that corresponds with FACT subunit SSRP1 tagged with a green fluorescent protein from the nucleoplasm and the nucleoli to chromatin (middle row, right to left panels). The ability to cause “chromatin damage” correlates better with anticancer potency of small molecules than their DNA damage capability, suggesting that it plays an important role in the anticancer activity of DNA binding small molecules. Bottom, a superposition of images in the two top rows. For details, see article by Nesher and colleagues on page 1431.