ИСТИНА

This study investigates the effects of several epigenetically active compounds on PARP1 functional activity, including its DNA-binding and catalytic properties. The examined compounds include natural bioactive substances, particularly plant polyphenols, as well as the synthetic agent curaxin CBL0137. Nucleosomes were used as an experimental model, as their relative simplicity allows for the study of key chromatin processes, such as transcriptional regulation and interactions with DNA-binding proteins. Furthermore, we characterized the activity of reference PARPi (olaparib and veliparib) on engineered nucleosomes containing both histone variants (H3.3 substitution for canonical H3, H2A.Z replacement of H2A) and specific epigenetic marks, notably including H3K56ac-mimetic modifications. Advanced biochemical and biophysical methods were employed to assess their impact on PARP1, including electrophoretic mobility shift assays (EMSA), Western blotting, and single-particle FRET microscopy (spFRET).