Molecular biology of the cell, 2021-11, Vol.32 (21), p.ar15-ar15
2021
Details
- Autor(en) / Beteiligte
- Titel
- Cdc7-mediated phosphorylation of Cse4 regulates high-fidelity chromosome segregation in budding yeast
- Ist Teil von
- Molecular biology of the cell, 2021-11, Vol.32 (21), p.ar15-ar15
- Ort / Verlag
- United States: The American Society for Cell Biology
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Faithful chromosome segregation maintains chromosomal stability as errors in this process contribute to chromosomal instability (CIN), which has been observed in many diseases including cancer. Epigenetic regulation of kinetochore proteins such as Cse4 (CENP-A in humans) plays a critical role in high-fidelity chromosome segregation. Here we show that Cse4 is a substrate of evolutionarily conserved Cdc7 kinase, and that Cdc7-mediated phosphorylation of Cse4 prevents CIN. We determined that Cdc7 phosphorylates Cse4 in vitro and interacts with Cse4 in vivo in a cell cycle-dependent manner. Cdc7 is required for kinetochore integrity as reduced levels of -associated Cse4, a faster exchange of Cse4 at the metaphase kinetochores, and defects in chromosome segregation, are observed in a strain. Phosphorylation of Cse4 by Cdc7 is important for cell survival as constitutive association of a kinase-dead variant of Cdc7 ( ) with Cse4 at the kinetochore leads to growth defects. Moreover, phospho-deficient mutations of Cse4 for consensus Cdc7 target sites contribute to CIN phenotype. In summary, our results have defined a role for Cdc7-mediated phosphorylation of Cse4 in faithful chromosome segregation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1059-1524eISSN: 1939-4586DOI: 10.1091/mbc.E21-06-0323Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8693968
- Format
- –
- Schlagworte
- Cell Cycle Proteins - metabolism, Cell Cycle Proteins - physiology, Centromere - metabolism, Centromere Protein A - metabolism, Chromatin - metabolism, Chromosomal Instability, Chromosomal Proteins, Non-Histone - genetics, Chromosomal Proteins, Non-Histone - metabolism, Chromosomal Proteins, Non-Histone - physiology, Chromosome Segregation - physiology, Chromosomes - metabolism, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, DNA-Binding Proteins - physiology, Epigenesis, Genetic, Histones - metabolism, Kinetochores - metabolism, Nuclear Proteins - metabolism, Phosphorylation, Protein Serine-Threonine Kinases - metabolism, Protein Serine-Threonine Kinases - physiology, Saccharomyces cerevisiae - metabolism, Saccharomyces cerevisiae Proteins - genetics, Saccharomyces cerevisiae Proteins - metabolism, Saccharomyces cerevisiae Proteins - physiology