Abstract
Centromeric CENP-A, a variant of histone H3, plays a central role in proper chromosome segregation and its function is highly conserved among different species. In most species with regional centromeres, an active centromere relies not on defined DNA sequences, but on the presence of CENP-A proteins in centromeric nucleosomes. CENP-A is proposed to be the non-DNA indicator (epigenetic mark) that defines proper centromere assembly and function. Recently, many post-translational modifications (PTMs) of CENP-A and their functions have been reported. They revealed the importance of the functions of CENP-A PTMs in CENP-A deposition at centromeres, proteolysis/protein stability, and recruitment of other centromere-kinetochore proteins. Ubiquitylation and sumoylation by E3 ligases regulate multiple functions, including proteolysis and signaling, and play important roles in the cell cycle and mitotic control. Recently, the function of E3 ligase that ubiquitylates/sumoylates and controls CENP-A protein has emerged as an important regulatory paradigm in different species. Many have reported the importance of CENP-A ubiquitylation and sumoylation in CENP-A deposition at centromeres and for protein stability, which is regulated by specific E3 ligases. Therefore, here we summarize what is known about the E3 ligases for CENP-A ubiquitylation and sumoylation and their biological functions and significance in different species.
Highlights
During cell division, proper chromosome segregation must be achieved to avoid unequal distribution of chromosomes to daughter cells
They showed that partner of paired (Ppa) depletion results in increased CenH3CID levels, and Ppa physically interacts with CenH3CID through the CATDCID and regulates CenH3CID stability in Drosophila [44, 118]
We reported that mono- or di-ubiquitylation of CENP-A K124 is required for CENP-A deposition at the centromere [35] (Figure 2, right)
Summary
Proper chromosome segregation must be achieved to avoid unequal distribution of chromosomes to daughter cells. In most species with regional centromeres (see the previous chapter for an exception of the budding yeast Saccharomyces cerevisiae that has genetically defined point centromeres), centromere identity relies not on a defined DNA sequence, but on the presence of a special nucleosome that contains a specific histone-like protein called CENP-A. Yeast suppressor of chromosome missegregation protein 3 (Scm3) [29] (previous chapter, Figure 1; Table 1) is a distant counterpart of human Holliday junction recognition protein (HJURP) (Figures 2 and 3; Table 1), and they are CENP-A (CenH3)-specific chromatin assembly factors [29, 41–43]. Many post-translational modifications of CENP-A and their functions have been reported [45] They revealed the importance of these changes in CENP-A deposition at centromeres, proteolysis/protein stability, and recruitment of the CCAN (constitutive centromere-associated network) proteins [45]. E3 ligase for fission yeast (Schizosaccharomyces pombe) CENP-ACnp and its function
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