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

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.
Mesh Terms:
Amino Acid Sequence, Centromere, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Euchromatin, 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, Ubiquitin-Protein Ligases, Ubiquitination
Mol. Cell
Date: Nov. 12, 2010
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