Abstract
Our understanding of the structure and function of kinetochores has advanced dramatically over the past 10 years, yet how the plus end of spindle microtubules interacts with the kinetochore and establishes amphitelic attachment for proper sister chromatid segregation remains unresolved. However, several recent reports from different organisms have shed new light on this issue. A key player in microtubule-kinetochore interaction is the conserved Ndc80 outer kinetochore complex. In both yeast and human cells in particular, a ubiquitous internal ‘loop’ found in the Ndc80 molecule interrupting its C-terminal coiled-coil domain plays critical roles in protein-protein interaction, by recruiting microtubule-binding proteins to ensure proper kinetochore-microtubule attachment. In this commentary, we summarise the recent progress made and discuss the evolutionary significance of this loop’s role in microtubule dynamics at the kinetochore for accurate chromosome segregation.
Highlights
Main text and discussionThe Ndc80 loop and its binding partners Structural studies have revealed that the Ndc80 complex has a dumbbell-like architecture consisting of an internal rod-shaped coiled-coil structure and a globular domain on each end [4,5]
By using specific ndc80 mutants that contain mutations within the loop in Saccharomyces cerevisiae, the Tanaka lab showed that this region facilitates binding of the Dam1 kinetochore complex to the Ndc80 complex (Figure 1, left)
This binding is essential for the conversion of lateral microtubule binding to end-on binding, which is a prerequisite for proper chromosome segregation [9]
Summary
The kinetochore complex attaches to the mitotic spindle to ensure accurate chromosome segregation [1,2,3]. The Ndc80/Hec complex, which is part of the KMN network (the KNL1/Mis complex/Ndc complex), is composed of a heterotetramer consisting of Ndc80/Hec, Nuf, Spc and Spc25 [1,4]. This complex is situated in the outer kinetochore and directly interacts with the microtubule [2,5]. How the kinetochore establishes stable amphitelic attachment to the dynamic plus end of the spindle microtubule during mitotic progression remained largely unknown
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