Cse4 gets a kiss-of-death from Psh1.

566 Cell Cycle Volume 10 Issue 4 Chromosome segregation is a key step to ensure the genetic material is equally distributed between the two daughter cells during cell division. Accuracy of this process is ensured by microtubule attachment to properly assembled kinetochores. The kinetochore is a massive protein complex formed at centromeres. The location of its formation is specified by the centromeric nucleosome, a special nucleosome that contains a histoneH3 variant, called generically CenH3 or specifically CENP-A (humans), CID (D. melanogaster) or Cse4 (S. cerevisiae). How CenH3 is confined to centromeric nucleosomes is a mystery. In budding yeast, the centromere is specified by a single nucleosome, making it a simple system to study this problem. In 2004, ubiquitin-mediated proteolysis was identified as a means of controlling Cse4 levels. In the proposed model, Cse4 that is misincorporated into euchromatin is ubiquitylated and targeted for proteasome-assisted degradation while Cse4 at centromeres is protected from such a mechanism by the kinetochore. The modulators of Cse4 ubiquitylation were unknown until recently our group and Ranjitkar et al. reported the discovery of an E3 ubiquitin-ligase named Psh1 (Pob3/Spt16 histone associated). Psh1 co-purifies and physically interacts with Cse4, but not with histone-H3. With the help of Ubc8 as the ubiquitin-conjugating enzyme (E2), Psh1 specifically ubiquitylates free Cse4 and Cse4-octamers in vitro. Deletion of PSH1 stabilizes Cse4 in vivo. How is Psh1-assisted Cse4 degradation regulated? Psh1 has three main domains: (1) a RING finger, (2) a Zinc finger and (3) a highly acidic domain. The RING finger of Psh1 is critical for the physical Cse4 gets a kiss-of-death from Psh1