CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere
Copyright policy )CENP-A K124 Ubiquitylation Is Required for CENP-A Deposition at the Centromere
CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) and CENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that "signaling" ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.
- The Ohio State University United States
- Nationwide Children's Hospital United States
- St. Jude Children's Research Hospital United States
- The Research Institute at Nationwide Children's Hospital United States
COP9 Signalosome Complex, Chromosomal Proteins, Non-Histone, Lysine, Blotting, Western, Centromere, Molecular Sequence Data, Fluorescent Antibody Technique, Cullin Proteins, Autoantigens, Nucleosomes, Histones, Immunoenzyme Techniques, Chromosome Segregation, Humans, Amino Acid Sequence, Carrier Proteins, Luciferases, Cells, Cultured, Centromere Protein A, Developmental Biology, HeLa Cells
COP9 Signalosome Complex, Chromosomal Proteins, Non-Histone, Lysine, Blotting, Western, Centromere, Molecular Sequence Data, Fluorescent Antibody Technique, Cullin Proteins, Autoantigens, Nucleosomes, Histones, Immunoenzyme Techniques, Chromosome Segregation, Humans, Amino Acid Sequence, Carrier Proteins, Luciferases, Cells, Cultured, Centromere Protein A, Developmental Biology, HeLa Cells
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