C-Terminal Motifs of the MTW1 Complex Cooperatively Stabilize Outer Kinetochore Assembly in Budding Yeast

Ghodgaonkar-Steger, Medini; Potocnjak, Mia; Zimniak, Tomasz; Fischböck-Halwachs, Josef; Solis‐Mezarino, Victor; Singh, Sylvia; Speljko, Tea; Hagemann, Götz; Drexler, David; Witte, Gregor; Herzog, Franz

doi:10.1016/j.celrep.2020.108190

Cited by 5 publications

(16 citation statements)

References 68 publications

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“…This is consistent with observations reported previously with Zwint1, human orthologue of Kre28 [21]. Our FRET data are also in accordance with previously published biochemical and cell biological studies [13, 14, 21]. Interestingly, we could not determine the FRET between Kre28-C and components of Mtw1 complex, because strains expressing the fluorescent fusions were inviable.…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, we could not determine the FRET between Kre28-C and components of Mtw1 complex, because strains expressing the fluorescent fusions were inviable. The fluorescent tags most likely disrupt interactions between Spc105/Kre28 and the Mtw1 complex, which results in synthetic lethality [13].…”

Section: Discussionmentioning

confidence: 99%

“…It was also not sufficient to support cell viability in absence of wild-type Kre28. Much to our surprise, even after taking the data of Herzog lab into consideration, when we maintained the two binding sites of Spc105 (kre28 128–169 and kre28 229–259 ) in our kre28 cassette (kre28 Δ1-126 ) [13], we did not see any kinetochore localization. After considering these data we can conclude that full length Kre28 is essential for its localization and for full kinetochore recruitment of Spc105.…”

Section: Discussionmentioning

confidence: 99%

“…Still, the specific function of Kre28 remains unclear. How Kre28 localizes within the kinetochore-microtubule attachment site is also unknown [13][14][15]. Here we define the localization of Kre28 in kinetochore-microtubule attachment sites of bioriented kinetochores and elucidate its functional role.…”

Section: Introductionmentioning

confidence: 96%

“…Kre28 is an orthologue of human Zwint1, C. elegans Kbp-5, and S. pombe Sos7 [9–12]. Previous studies, using in-vitro and in-vivo experiments, provide some insights in how Spc105 and Kre28 are assembled at the kinetochores, but it is not clear what the specific function of Kre28 is, how it is aligned in the kinetochore microtubule attachment sites and how it contributes to kinetochore functions [13–15]. Here we investigate the localization of Kre28 in kinetochore microtubule attachment sites of bioriented kinetochores and its role in kinetochore microtubule attachment and spindle assembly checkpoint activation in yeast.…”

Section: Introductionmentioning

confidence: 99%

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Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore

Roy

Sim

Han

et al. 2021

Preprint

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Kinetochores are macromolecular protein assemblies that attach sister chromatids to spindle microtubules and mediate accurate chromosome segregation during mitosis. The outer kinetochore consists of the KMN network, a protein super complex made of Knl1 (yeast Spc105), Mis12 (yeast Mtw1) and Ndc80 (yeast Ndc80), which harbors sites for microtubule binding. Within the KMN network, Spc105 acts as interaction hub of components involved in spindle assembly checkpoint (SAC) signaling. It is known that Spc105 forms a complex with kinetochore component Kre28. However, where Kre28 physically localizes in the budding yeast kinetochore is not clear. The exact function of Kre28 at the kinetochore is also unknown. Here, we reveal how Spc105 and Kre28 interact and how they are organized within bioriented yeast kinetochores using genetics and cell biological experiments. We also identify the interaction interface between the two proteins and show that this interaction is important for Spc105 protein turn-over and essential for their mutual recruitment at the kinetochores. We created several truncation mutants of kre28 that do not localize at the kinetochores and so cannot mediate Spc105 loading at the kinetochores. When we over-expressed these mutants, they could sustain the cell viability even though failed to facilitate proper SAC activation and/or error correction. Thus, we inferred that Kre28 indirectly contributes to chromosome biorientation and high-fidelity segregation by regulating Spc105 localization at the kinetochores.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore

Roy

Sim

Han

et al. 2021

Preprint

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Plasticity in centromere organization and kinetochore composition: Lessons from diversity

Ishii

Akiyoshi

2022

Current Opinion in Cell Biology

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Impact of KMN network genes on progression and prognosis of non-small cell lung cancer

et al. 2021

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The Knl1-Mis12-Ndc80 (KMN) network genes (including KNL, MIS12 and NDC80 complexes) encode a highly conserved network of protein complexes that act in cell mitosis. In recent years, multiple studies revealed that KMN network genes also play a vital role in tumor appearance and growth. However, the role of the KMN gene network in non-small cell lung cancer (NSCLC) remains unknown. In this study, we analyzed the effects of KMN genes expression and clinical phenotype in patients with lung adenocarcinoma (LUAD). The expression of KMN network genes and related clinical information was extracted from The Cancer Genome Atlas. The samples were classified into cluster I and II by consistent clustering. We analyzed the gene distribution by principal component analysis, and the potential risk characteristics were analyzed using the least absolute shrinkage and selection operator Cox regression algorithm. Univariate and multivariate Cox regression analyses were used to analyze the clinical information. The Database for Annotation, Visualization, and Integrated Discovery, Gene MANIA and gene set enrichment analysis were used to analyze function and correlation among genes of the KMN network. The expression levels of nine out of ten KMN genes were significantly up-regulated in LUAD and were associated with poor overall survival (OS). Higher expression of NDC80 and KNL1 was related to low OS in both univariate and multivariate analyses. According to two independent prognostic KMN network genes (KNL1 and NDC80), a risk signature was established to predict the prognosis of patients with LUAD. Additionally, the genes NDC80 and KNL1 were considerably enriched in pathways associated with signaling pathways, biological processes, and the cell cycle. The results indicate that KMN network genes are intimately related to lung adenocarcinoma. KMN network genes are involved in the malignant process of LUAD. Assessment of NDC80 and KNL1 might be helpful for prognostic stratification and treatment strategy development. Anti-Cancer Drugs 33: e398-e408 Copyright

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C-Terminal Motifs of the MTW1 Complex Cooperatively Stabilize Outer Kinetochore Assembly in Budding Yeast

Cited by 5 publications

References 68 publications

Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore

Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore

Plasticity in centromere organization and kinetochore composition: Lessons from diversity

Impact of KMN network genes on progression and prognosis of non-small cell lung cancer

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