A role for β-1,6- and β-1,3-glucans in kinetochore function in Saccharomyces cerevisiae.

CHROMOSOMES; DNA; CARBOHYDRATE metabolism; GENETIC mutation; GENETICS; GLYCOSYLATION; CELL physiology; PLASMIDS; YEAST; CELL cycle; CELLULAR signal transduction; GENE expression; BETA-glucans; SACCHAROMYCES; PLANT extracts; NUTRITIONAL status

Chromosome segregation is crucial for the faithful inheritance of DNA to the daughter cells after DNA replication. For this, the kinetochore, a megadalton protein complex, assembles on centromeric chromatin containing the histone H3 variant CENP-A, and provides a physical connection to the microtubules. Here, we report an unanticipated role for enzymes required for β-1,6- and β-1,3-glucan biosynthesis in regulating kinetochore function in Saccharomyces cerevisiae. These carbohydrates are the major constituents of the yeast cell wall. We found that the deletion of KRE6 , which encodes a glycosylhydrolase/ transglycosidase required for β-1,6-glucan synthesis, suppressed the centromeric defect of mutations in components of the kinetochore, foremost the NDC80 components Spc24 , Spc25 , the MIND component Nsl1 , and Okp1 , a constitutive centromere-associated network protein. Similarly, the absence of Fks1 , a β-1,3-glucan synthase, and Kre11 / Trs65 , a TRAPPII component, suppressed a mutation in SPC25. Genetic analysis indicates that the reduction of intracellular β-1,6- and β-1,3-glucans, rather than the cell wall glucan content, regulates kinetochore function. Furthermore, we found a physical interaction between Kre6 and CENP-A/ Cse4 in yeast, suggesting a potential function for Kre6 in glycosylating CENP-A/ Cse4 or another kinetochore protein. This work shows a moonlighting function for selected cell wall synthesis proteins in regulating kinetochore assembly, which may provide a mechanism to connect the nutritional status of the cell to cell-cycle progression and chromosome segregation. [ABSTRACT FROM AUTHOR]

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