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Structural and functional analysis of the kinetochore – chromatin interface in Saccharomyces cerevisiae

Subject Area General Genetics and Functional Genome Biology
Cell Biology
Term from 2018 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 411741701
 
Final Report Year 2024

Final Report Abstract

We report an unanticipated role for enzymes required for b-1,6 and b-1,3 glucan biosynthesis in regulating kinetochore function in Saccharomyces cerevisiae. These carbohydrates are the major constituents of the yeast cell wall. Deletion of KRE6 - a glycosylhydrolase critical for b-1,6 glucan synthesis suppressed the defects caused by mutations in components of the kinetochore. Our extensive genetic analyses revealed that there was a trend in the suppression pattern in that several mutations of outer kinetochore components were strongly suppressed, whereas mutations of inner kinetochore components were either unaffected, and the growth defect of a temperature sensitive CSE4 allele was enhanced. We also found out that the absence of other genes involved in cell wall synthesis such as FKS1- b-1,3 glucan synthase, and KRE11- a TRAPPII component, suppressed the growth defects with the mutation in SPC25. Probably, the reduction of intracellular b-1,6 and b -1,3 glucan regulates kinetochore function. Interestingly, we found a physical interaction between Kre6 and Cse4 in yeast, suggesting a potential function for Kre6 in glycosylating Cse4 or another kinetochore protein. Altogether, our work suggests a potential role for carbohydrate synthesis factors and carbohydrate modification of kinetochore proteins in chromosome biology.

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