Research Article: Modeling the functions of condensin in chromosome shaping and segregation

Date Published: June 18, 2018

Publisher: Public Library of Science

Author(s): Yuji Sakai, Atsushi Mochizuki, Kazuhisa Kinoshita, Tatsuya Hirano, Masashi Tachikawa, Alexandre V. Morozov

Abstract: The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.

Partial Text: The assembly of rod-shaped chromosomes is one of the most dramatic events occurring during the eukaryotic cell cycle. Upon entry into mitosis, the mass of chromatin distributed within the interphase nucleus is converted into a discrete set of rod-shaped chromosomes. This process, commonly referred to as mitotic chromosome condensation, helps to relieve the entanglements created between duplicated sister chromatids and between different chromosomes, thereby ensuring the equal segregation of genetic information into daughter cells. Despite the long history of chromosome research, the mechanistic details of how such rod-shaped chromosomes might be assembled from long DNA molecules and a myriad of associated proteins remain a substantial mystery [1, 2].

In the current study, we modeled the action of condensins in chromosome shaping and segregation, based on the assumption that they have two molecular activities: chromatin loop formation and inter-condensin attractions [5]. The former function is modeled as the loop-holding force Floop and the latter is modeled as the attraction force Fcond with the threshold distance Δ. We calculated the asphericity and segregation speed as the order parameters for chromosome shaping and segregation, respectively, and show that both strongly depend on the parameters of the presumed condensin activities. It is noteworthy that although both loop formation and inter-condensin attractions occur locally, they can make discrete contributions to the global conformational changes of chromosomes. Our results also demonstrate that the asphericity (i.e., rod-shaping) and segregation speed have a strong positive correlation, implying that the shaping and segregation of mitotic chromosomes might be controlled by a common underlying mechanism. This correlation greatly extends the interpretation of our recent result showing that elongation and compaction increase the segregation speed of entangled polymers [20].