Fig. 5: Schematic representation of the proposed model for the role of PICH in UFB dissolution.

i At the early stages of mitosis, when low tensions (represented by black horizontal arrows) are exerted on sister chromatid (purple and light blue) entanglements, nucleosome-nucleosome interactions are disrupted and nucleosome outer turns are unwrapped. This results in nucleosome-free dsDNA regions between neighboring inner-turn nucleosomes. The bare dsDNA regions will be readily bound by PICH (green). Histone octamers are depicted in red. ii PICH utilizes ATP hydrolysis to extrude DNA loops. iii The ATP-dependent loop extrusion by PICH, and likely the accompanying torsional stress, will facilitate inner-turn unwrapping of the nucleosomes on the UFB, resulting in loss of H2A/H2B dimers and thus, the formation of H3-H4 tetramers (pink). Consequently, an increasing amount of nucleosome-free DNA becomes available for PICH to bind to. iv Bound PICH can slide remaining histones (e.g., H3 and/or H4) along the UFB. v PICH-induced histone sliding increases the accessibility of the DNA entanglement, allowing additional PICH to bind. vi Binding of PICH to the DNA entanglement results in a sufficient recruitment platform for the BTRR dissolvasome and stimulation of TopoIIα (not shown), which, in turn, (vii) facilitates the unlinking of the DNA entanglement and, therefore, a timely dissolution of the UFB.