Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Kinetochore–microtubule interactions: steps towards bi-orientation

Funder Wellcome Charity-funded
Recipient organisation University of Dundee
Funding £1.5M
Period Dec 2020 — Nov 2025

In plain English

AI plain-English summary

Every time a human cell divides, it must pull its duplicated chromosomes apart into two identical sets—and when that process goes wrong, the result can be cancer or a child born with a congenital disorder. This project investigates the very first moments of that process, when the cell’s internal machinery—specifically, the protein structures called kinetochores—grabs hold of the microtubule cables that will yank the chromosomes apart. The researchers want to understand how those initial attachments are made, how the cell detects and corrects mistakes, and how it locks in the correct, tension-bearing connections that ensure each daughter cell gets a complete genome. This is fundamental science, not applied medicine. There is no immediate diagnostic or therapeutic payoff. But chromosome mis-segregation is a root cause of aneuploidy—abnormal chromosome numbers—which drives many cancers and developmental disorders. By revealing the molecular steps that normally prevent such errors, this work could eventually point toward targets for drugs that make cancer cells more prone to lethal mis-segregation, or toward understanding why some pregnancies miscarry due to chromosomal mistakes. The researchers use budding yeast, a simple organism where each kinetochore attaches to a single microtubule, making the mechanics far easier to study than in human cells. The same core mechanisms are evolutionarily conserved, so what they learn in yeast will apply directly to human biology.

View original technical description
To maintain genetic integrity, eukaryotic cells must properly segregate sister chromatids to opposite spindle poles during mitosis. This process has important medical relevance because chromosome mis-segregation plays causative roles in human diseases such as cancers and congenital disorders, which are often characterized by chromosome instability and aneuploidy. For proper chromosome segregation, it is vital to establish correct kinetochore–microtubule interaction in early mitosis, prior to segregation. We will investigate how kinetochores initially interact with microtubules on the mitotic spindle and how errors in kinetochore–microtubule interactions are resolved to establish correct interactions. In particular, we will address the following questions: A) What are the molecular mechanisms regulating the kinetochore–microtubule interface during early mitosis? B) What are the mechanisms resolving errors in kinetochore–microtubule interactions and stabilising correct interactions in a tension-dependent manner? To address evolutionarily conserved mechanisms, we use budding yeast as a model organism because, in this organism, a single microtubule attaches to a single kinetochore in metaphase – this considerably simplifies our analyses. We use methods in cell biology, molecular genetics, biochemistry and computer simulation, and address not only molecular mechanisms but also the biological significance of step-by-step development in the kinetochore–microtubule interaction.

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Researchers

Tomoyuki Tanaka (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular mechanisms regulating the kinetochore-microtubule interaction in mitosis.
Molecular mechanisms of kinetochore-microtubule interaction
Mechanisms ensuring sister kinetochore bi-orientation on the mitotic spindle
Mechanisms orienting chromosomes in mitosis and meiosis.
Cooperativity and forces in molecular interactions governing chromosome stability

Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.