Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly. 2023

Stephen M Hinshaw, and Yun Quan, and Jiaxi Cai, and Ann L Zhou, and Huilin Zhou
Stanford Cancer Institute, Stanford School of Medicine, 1291 Welch Road, Stanford, CA 94305, USA. Electronic address: hinshaw@stanford.edu.

Kinetochores control eukaryotic chromosome segregation by connecting chromosomal centromeres to spindle microtubules. Duplication of centromeric DNA necessitates kinetochore disassembly and subsequent reassembly on nascent sisters. To search for a regulatory mechanism that controls the earliest steps of this process, we studied Mif2/CENP-C, an essential basal component of the kinetochore. We found that phosphorylation of a central region of Mif2 (Mif2-PEST) enhances inner kinetochore assembly. Eliminating Mif2-PEST phosphorylation sites progressively impairs cellular fitness. The most severe Mif2-PEST mutations are lethal in cells lacking otherwise non-essential inner kinetochore factors. These data show that multi-site phosphorylation of Mif2/CENP-C controls inner kinetochore assembly.

UI MeSH Term Description Entries
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002503 Centromere The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. Centromeres
D002868 Chromosomal Proteins, Non-Histone Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens. Non-Histone Chromosomal Proteins,Chromosomal Proteins, Non Histone,Chromosomal Proteins, Nonhistone,Non-Histone Chromosomal Phosphoproteins,Chromosomal Phosphoproteins, Non-Histone,Non Histone Chromosomal Phosphoproteins,Non Histone Chromosomal Proteins,Nonhistone Chromosomal Proteins,Proteins, Non-Histone Chromosomal
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000076247 Centromere Protein A A 17 kDa, centromeric, poly(ADP)-ribose binding protein that is structurally similar to HISTONE H3 and localizes to NUCLEOSOMES within the CENTROMERE; specifically within the region that binds KINETOCHORES, where it replaces histone H3. It plays a critical role in recruiting kinetochore proteins and progression through MITOSIS, chromosome segregation, and CYTOKINESIS. It also binds sera from patients with some scleroderma-like AUTOIMMUNE DISEASES. CENP-A Protein,CENPA Protein,Centromere Autoantigens 17K,Centromere Protein 17K,Autoantigens 17K, Centromere,CENP A Protein
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D018386 Kinetochores Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle. Kinetochore
D029701 Saccharomyces cerevisiae Proteins Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. Baker's Yeast Proteins,S cerevisiae Proteins

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