Valerio Sorichetti

Electrostatic "patchy" interactions drive chromosome clustering in eukaryotes

Individualization and clustering of chromosomes, fundamental processes for the eukaryotic cell division, have been shown to be regulated by the surfactant-like protein Ki-67 [1]. This protein, which coats the chromosome surface forming a brush, is negatively charged (phosphorylated) in early mitosis, thus promoting repulsion between the chromosomes and individualization. In mitotic exit, however, it undergoes dephosphorylation, becoming positively charged and generating attraction between the chromosomes, mediated by negatively charged RNA [1]. This results in RNA-mediated liquid-liquid phase separation of Ki-67. The effectiveness of this RNA-mediated attraction is greatly increased by the presence of a localized charge "patch" on Ki-67, which has been shown to be remarkably well conserved in different organisms. In this work, we show using computer simulations of a coarse-grained model that polymer-mediated attraction between two electrically charged polymer brushes is greatly enhanced when the brushes have highly charged "patches". Our model is found to be in good agreement with in vivo data. The effectiveness of this attraction mechanism is proposed to be essential for chromosome clustering in eukaryotes and at the basis of its ubiquity in different organisms.

[1] A. Hernandez-Armendariz, V. Sorichetti, Y. Hayashi, A. Šarić and S. Cuylen-Haering, Ki-67 clusters chromosomes during mitotic exit by establishing an RNA-based liquid phase on their surface (in review)