Minimal Ingredients for Coupled Spindle Assembly and Chromosome Bi-orientation in a Computational Model of Fission Yeast Mitosis

Abstract

Mitosis ensures the proper segregation of chromosomes into daughter cells, which is accomplished by the mitotic spindle. During fission-yeast mitosis, chromosomes establish bi-orientation as the bipolar spindle assembles, meaning that sister kinetochores become attached to microtubules whose growth was initiated by sister poles. This process must also correct erroneous attachments made by the kinetochores during the attachment process. Our goal is to build a 3D computational model of spindle assembly based on a realistic description of microtubule, kinetochore, and chromosome dynamics, in order to interrogate the role of specific mechanisms in these chromosome bi-orientation and error correction processes. We have added chromosomes to our previous computational model of spindle assembly, which included microtubules, a spherical nuclear envelope, motor proteins, crosslinking proteins, and spindle pole bodies (centrosomes). In the new model, each chromosome is represented by a pair of sister chromatids, and sister kinetochores are represented as chromatid-associated polygons. In preliminary work, we have explored the mechanical properties of kinetochores and their interactions with microtubules that achieve amphitelic spindle attachments at high frequency. A plausible set of minimal assumptions yields simulations that generate chromosome attachment errors, but resolve them, much as normal chromosomes do.