Cell cycle adaptation to aneuploidy:
How do cells adapt to carrying an extra chromosome?

Collaborators: Gautam Dey (EMBL) & Gavin Sherlock (Stanford)

Background

All eukaryotes must rapidly and reproducibly reorganise and partition their genome each cell cycle, in a process carefully coordinated with growth, nuclear dynamics, and cell cycle signalling. However, genome organisation (chromosome number, size and orientation within the nucleus) and cell cycle architecture (permeabilisation of the nucleus, distribution of cell cycle phases, presence of checkpoints) can vary massively between species, making it difficult to assess the driving forces and evolutionary constraints underlying the relationship between structural features of the genome and the cell that encases it.

Project

How do cells adapt to carrying an extra chromosome?

Here, we are interested in understanding one key aspect of this relationship: how do cells respond to the challenge of packaging extra DNA? We aim to address this in yeast that are forced to carry an extra chromosome with minimal transcriptional potential, using a combination of experimental evolution (led by the Sherlock Lab at Stanford) and cell biological profiling (in the Dey Group at EMBL). What solutions do cells evolve to cope with aneuploidy, independent of problems with gene expression and dosage? What impact does an extra chromosome have on the size and organisation of the nucleus, the chromosome segregation machinery, and the cell cycle regulatory network?

References:
Levy, S. F., Blundell, J. R., Venkataram, S., Petrov, D. A., Fisher, D. S. and Sherlock, G. (2015). Quantitative evolutionary dynamics using high-resolution lineage tracking. Nature 519, 181–186.

Torres, E. M., Sokolsky, T., Tucker, C. M., Chan, L. Y., Boselli, M., Dunham, M. J. and Amon, A. (2007). Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science (80-. ). 317, 916–924.

Torres, E. M., Dephoure, N., Panneerselvam, A., Tucker, C. M., Whittaker, C. A., Gygi, S. P., Dunham, M. J. and Amon, A. (2010). Identification of aneuploidy-tolerating mutations. Cell 143, 71–83.

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Interested in finding out more working at the interface of evolution and cell biology? Get in touch, we would love to hear from you!