Chapters authored
E3 Ligase for CENP-A (Part 1)
CENP-A is a centromere-specific histone H3 variant that is required to ensure kinetochore assembly for proper chromosome segregation and its function is highly conserved among different species including budding yeast, Saccharomyces cerevisiae. The budding yeast Saccharomyces cerevisiae has genetically defined point centromeres, unlike other eukaryotes. Although, most eukaryotic centromeres are maintained epigenetically, currently only budding yeast S. cerevisiae centromeres are known to be genetically specified by DNA sequence, The small size and sequence specificity of the budding yeast centromere has made yeast a powerful organism for its study in many aspects. Many post-translational modifications (PTMs) of CENP-A and their functions have been recently reported, and studies with budding yeast are providing insights into the role of CENP-A/Cse4 PTMs in kinetochore structure and function. Multiple functions are controlled especially by ubiquitylation and sumoylation by E3 ligases that control CENP-A protein has initially emerged in the budding yeast as an important regulatory mechanism. Here we focus on what is known about the budding yeast E3 ligases for CENP-A/Cse4 ubiquitylation and sumoylation and their biological functions and significance.
Part of the book: Hydrolases
E3 Ligase for CENP-A (Part 2)
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.
Part of the book: Hydrolases