Cohesin in stress: Effect of stress on sister chromatid cohesion and genome organization

Stress conditions induce many cellular changes in the transcriptome and proteome. However, very little is known about the effect of stress on the 3D organization of chromatin and its stability. An intriguing report suggested that the immediate response of yeast cells to stress is aneuploidy. The Structural Maintenance of Chromosome (SMC) complex cohesin is involved in determining the 3D structure of chromatin and is essential to ensure chromosome segregation. We hypothesized that stress-induced aneuploidy is linked to the temporary inactivation of cohesin. We found that after exposing yeast cells to stress, the mRNAs of two cohesin important regulators, Pds5, and Scc2 are downregulated. Furthermore, we discovered that after stress the Pds5 protein is relocalized from the nucleus to the cytoplasm. Pds5 maintains the stability of cohesin by protecting the Mcd1 from ubiquitination and degradation. Indeed, our preliminary analysis shows that in stress Mcd1 levels decrease and as a result cohesin activity is expected to be compromised. Our work impacts current knowledge in two ways. It describes a new mechanism of induced genome instability in response to stress that may help cells adapt to new conditions. If this mechanism is conserved in human cells it might be relevant to genome instability in cancer cells. In addition, dissecting the effect of stress on cohesin and the 3D organization of the genome will provide new insights into the unknown interplay between these processes.