The Ndc80-Cdt1-Ska1 complex is a central processive kinetochore-microtubule coupling unit
Amit Rahi1, Manas Chakraborty1, Shivangi Agarwal
1Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
The Journal of Cell Biology
|June 2, 2023
Summary
The study reveals that Cdt1, a DNA replication factor, plays a crucial role in chromosome segregation by forming a complex with Ndc80 and Ska1 proteins to ensure stable kinetochore-microtubule attachments during cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Kinetochore-microtubule attachments are essential for accurate chromosome segregation during mitosis.
- The Ndc80 complex, Ska1 complex, and Cdt1 are known to be involved in these attachments, but the precise mechanism of stable coupling to dynamic microtubules remains unclear.
Purpose of the Study:
- To elucidate the role of Cdt1 in chromosome segregation and kinetochore-microtubule interactions.
- To investigate the mechanism by which the Ndc80 complex is stably coupled to dynamic spindle microtubule plus-ends.
Main Methods:
- Utilized a conditional auxin-inducible degron system to deplete Cdt1.
- Investigated the interaction between Cdt1 and Ska1.
- Analyzed the effect of Cdt1 phosphorylation by Cdk1 kinase.
- Performed in vitro microtubule binding assays with the Ndc80-Cdt1-Ska1 complex.
Main Results:
- Cdt1 has a function in chromosome segregation and kinetochore-microtubule interactions independent of its DNA replication licensing role.
- A direct interaction between Cdt1 and Ska1 is necessary for Cdt1 recruitment to kinetochores and microtubules.
- Cdt1 phosphorylation by Cdk1 is critical for Ska1 binding, kinetochore-microtubule attachments, and mitotic progression.
- Cdt1, Ndc80, and Ska1 form a tripartite complex that processively tracks dynamic microtubule plus-ends.
Conclusions:
- The Ndc80-Cdt1-Ska1 complex is a key molecular unit mediating processive microtubule tip-tracking by kinetochores.
- This complex ensures robust kinetochore-microtubule attachments, crucial for accurate chromosome segregation.
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