An E3 ubiquitin ligase prevents ectopic localization of the centromeric histone H3 variant via the centromere targeting domain.

Publication Type:

Journal Article


Molecular cell, Volume 40, Issue 3, p.455-64 (2010)


2010, Amino Acid Sequence, Basic Sciences Division, Center-Authored Paper, centromere, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Euchromatin, Genomics Core Facility, Histones, Molecular Sequence Data, Mutation, Peptide Elongation Factors, Protein Binding, Protein Isoforms, Protein Processing, Post-Translational, Protein Stability, Protein Structure, Tertiary, Protein Transport, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Shared Resources, Ubiquitin-Protein Ligases, UBIQUITINATION


Proper centromere function is critical to maintain genomic stability and to prevent aneuploidy, a hallmark of tumors and birth defects. A conserved feature of all eukaryotic centromeres is an essential histone H3 variant called CENP-A that requires a centromere targeting domain (CATD) for its localization. Although proteolysis prevents CENP-A from mislocalizing to euchromatin, regulatory factors have not been identified. Here, we identify an E3 ubiquitin ligase called Psh1 that leads to the degradation of Cse4, the budding yeast CENP-A homolog. Cse4 overexpression is toxic to psh1Δ cells and results in euchromatic localization. Strikingly, the Cse4 CATD is a key regulator of its stability and helps Psh1 discriminate Cse4 from histone H3. Taken together, we propose that the CATD has a previously unknown role in maintaining the exclusive localization of Cse4 by preventing its mislocalization to euchromatin via Psh1-mediated degradation.