ArticleThe EMBO journal2023
DASH/Dam1 complex mutants stabilize ploidy in histone-humanized yeast by weakening kinetochore-microtubule attachments.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Resolving translational challenges in cancer biology through yeast experimental evolution.Cancer metastasis reviews · 2026Review
- Tiny Yeast Comet 1-Dependent Polymers Suppress Taxol-Stabilized Microtubule Depolymerization Induced by Ice-Cold CaClInternational journal of molecular sciences · 2026Article
- Using Yeast Two-Hybrid Screening and Structural Modeling to Identify Candidate Hrr25 Kinase Interactors at the Meiotic Kinetochore inInternational journal of molecular sciences · 2026Article
- Article
- Microtubule dynamics are defined by conformations and stability of clustered protofilaments.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
- Gene loss and cis-regulatory novelty shaped core histone gene evolution in the apiculate yeast Hanseniaspora uvarum.Genetics · 2024Article
- Humanization reveals pervasive incompatibility of yeast and human kinetochore components.G3 (Bethesda, Md.) · 2023Article
- Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules.Science (New York, N.Y.) · 2023Article
- Experimental evolution for cell biology.Trends in cell biology · 2023Review
- Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast.Genetics · 2023Article
- The adaptive strategies of cells in the face of CIN.The EMBO journal · 2023Article
- DASH/Dam1 complex mutants stabilize ploidy in histone-humanized yeast by weakening kinetochore-microtubule attachments.The EMBO journal · 2023Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Forcing budding yeast to chromatinize their DNA with human histones manifests an abrupt fitness cost. We previously proposed chromosomal aneuploidy and missense mutations as two potential modes of adaptation to histone humanization. Here, we show that aneuploidy in histone-humanized yeasts is specific to a subset of chromosomes that are defined by their centromeric evolutionary origins but that these aneuploidies are not adaptive. Instead, we find that a set of missense mutations in outer kinetochore proteins drives adaptation to human histones. Furthermore, we characterize the molecular mechanism underlying adaptation in two mutants of the outer kinetochore DASH/Dam1 complex, which reduce aneuploidy by suppression of chromosome instability. Molecular modeling and biochemical experiments show that these two mutants likely disrupt a conserved oligomerization interface thereby weakening microtubule attachments. We propose a model through which weakened microtubule attachments promote increased kinetochore-microtubule turnover and thus suppress chromosome instability. In sum, our data show how a set of point mutations evolved in histone-humanized yeasts to counterbalance human histone-induced chromosomal instability through weakening microtubule interactions, eventually promoting a return to euploidy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.