Molecular mechanism targeting condensin for chromosome condensation

Wang, M., Robertson, D., Zou, J., Spanos, C., Rappsilber, J., and Marston, A.L.

By Elena Hein, Bird Lab

During mitosis, the genome needs to be accurately organised to prevent aneuploidy and associated genetic and cellular defects. The protein complexes cohesin and condensin are part of the Structural Maintenance of Chromosomes (SMC) protein family, and play a crucial role in chromosome organisation to ensure correct chromosome segregation during cell division.  Alongside cohesin and condensin, the pericentromeric adapter protein Shugoshin 1 (Sgo1) plays a key role in ensuring the accuracy of chromosome segregation. Sgo1 associates with the pericentromere region of chromosomes downstream of cohesin where it directs recruitment of a number of protein complexes, including condensin, to promote sister kinetochore biorientation. While the role of SMC proteins in organising chromosome architecture has been widely established, the molecular mechanisms that target and control the activity of SMC complexes remain unclear. 

In their paper, Wang et al. reveal how condensin is targeted to pericentromeric and ribosomal DNA (rDNA) regions in budding yeast, and find similarities that indicate conserved mechanisms of SMC regulation in other systems.  The authors identified a conserved sequence motif, termed CR1, which is found on Sgo1 and other condensin-recruiting chromatin proteins across phyla, and which was confirmed to bind directly to a conserved patch in the yeast condensin subunit Ycg1.  The interaction between Ycg1 and Sgo1, as well as between Ycg1 and another CR1-containing receptor protein Lrs4, were shown to drive condensin recruitment to pericentromeric and rDNA chromatin regions, respectively. 

Furthermore, the researchers found that establishment of correct chromosome biorientation and chromosomal arm condensation is dependent on the Ycg1 subunit and its interaction with Sgo1 and likely other CR1-motif containing proteins. 

Overall, this study provides the first molecular explanation of how condensin is targeted to specific chromatin domains to ensure accurate segregation, and suggests an overarching principle in SMC protein localisation and regulation.