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

**Authors:** Rucha Kshirsagar, Arno Munhoven, Tra My Tran Nguyen, Ann E Ehrenhofer-Murray

PMC · DOI: 10.1093/genetics/iyad195 · Genetics · 2023-11-10

## TL;DR

This study reveals that enzymes involved in yeast cell wall synthesis also play a role in kinetochore function, which is essential for proper chromosome segregation during cell division.

## Contribution

The paper discovers a novel regulatory role for β-1,6- and β-1,3-glucan biosynthesis enzymes in kinetochore function in yeast.

## Key findings

- Deletion of KRE6 suppresses centromeric defects in kinetochore components like NDC80 and MIND.
- Reduction of intracellular β-glucans, not cell wall content, regulates kinetochore function.
- Kre6 physically interacts with CENP-A/Cse4, suggesting a direct role in kinetochore regulation.

## Abstract

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.

## Linked entities

- **Genes:** KRE6 (beta-glucan synthesis-associated protein KRE6) [NCBI Gene 856287], NDC80 (NDC80 kinetochore complex component) [NCBI Gene 10403], SPC24 (SPC24 component of NDC80 kinetochore complex) [NCBI Gene 147841], SPC25 (SPC25 component of NDC80 kinetochore complex) [NCBI Gene 57405], NSL1 (NSL1 component of MIS12 kinetochore complex) [NCBI Gene 25936], OKP1 (Okp1p) [NCBI Gene 853090], SPC25 (SPC25 component of NDC80 kinetochore complex) [NCBI Gene 57405], FKS1 (1,3-beta-D-glucan synthase) [NCBI Gene 851055]
- **Proteins:** CENPA (centromere protein A), CSE4 (centromeric DNA-binding histone H3-like protein CSE4), KRE6 (beta-glucan synthesis-associated protein KRE6)
- **Species:** Saccharomyces cerevisiae (taxon 4932)

## Full-text entities

- **Genes:** HHT2 (histone H3) [NCBI Gene 855700], SPC24 (kinetochore-associated Ndc80 complex subunit SPC24) [NCBI Gene 855144], KRE6 (beta-glucan synthesis-associated protein KRE6) [NCBI Gene 856287] {aka CWH48}, SPC25 (kinetochore-associated Ndc80 complex subunit SPC25) [NCBI Gene 856738], OKP1 (Okp1p) [NCBI Gene 853090], CSE4 (centromeric DNA-binding histone H3-like protein CSE4) [NCBI Gene 853817] {aka CSL2}, TRS65 (Trs65p) [NCBI Gene 853076] {aka KRE11}, FKS1 (1,3-beta-D-glucan synthase) [NCBI Gene 851055] {aka CND1, CWH53, ETG1, GSC1, PBR1}, NSL1 (MIND complex subunit NSL1) [NCBI Gene 855843], NDC80 (kinetochore-associated Ndc80 complex subunit NDC80) [NCBI Gene 854662] {aka HEC1, TID3}

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11221361/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC11221361/full.md

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Source: https://tomesphere.com/paper/PMC11221361