Valerio Sorichetti, ISTA (Saric group) - Vienna

Valerio Sorichetti is a theoretical biophycist, expert in polymer simulations, currently postdoc at ISTA Vienna in Saric group, working on chromosome segregation.

https://vsorichetti.wordpress.com

Electrostatic “patchy” interactions drive chromosome clustering in
eukaryotes

Alberto Hernandez-Armendariz1,2, Valerio Sorichetti3, Yuki Hayashi1, Anđela Šarić3 and
Sara Cuylen-Haering1
1Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. 2Collaboration
for Joint PhD Degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany. 3Institute of Science
and Technology Austria, 3400 Klosterneuburg, Austria.

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
phosphorylated (and thus negatively charged) in early mitosis, promoting repulsion
between the chromosomes and individualization. In mitotic exit, however, it undergoes
dephosphorylation, becoming positively charged and leading to attraction between
chromosomes, mediated by the formation of “bridges” of negatively charged RNA [2].
The effectiveness of this RNA-mediated attraction is increased by the presence of a
localized charge patch on Ki-67, which is found 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
enhanced when the brushes have highly charged “patches”. We interpret this effect as
resulting from a competition between the loss of configurational entropy and the
enthalpic gain from opposite-charge attraction associated with the formation of the
RNA bridges. Our results are found to be in good qualitative 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 the ubiquity of Ki-67
orthologues displaying a charged patch in different organisms.

[1] S. Cuylen-Haering, M. Petrovic, A. Hernandez-Armendariz, M. W. G. Schneider, M. Samwer, C.
Blaukopf, Liam J. Holt and & Daniel W. Gerlich, Chromosome clustering by Ki-67 excludes cytoplasm
during nuclear assembly, Nature 587, 285–290 (2020)
[2] A. Hernandez-Armendariz, V. Sorichetti, Y. Hayashi, A. Šarić and S. Cuylen-Haering, A phase
transition mediates chromosome clustering during mitotic exit (submitted)

Contact : Daniel Jost