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Published on: June 6, 2017
Evolution and function of the mitotic checkpoint
Mathijs Vleugel1, Erik Hoogendoorn, Berend Snel
1Department of Medical Oncology, Department of Molecular Cancer Research and Cancer Genomics Centre, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Abstract:
The mitotic checkpoint evolved to prevent cell division when chromosomes have not established connections with the chromosome segregation machinery. Many of the fundamental molecular principles that underlie the checkpoint, its spatiotemporal activation, and its timely inactivation have been uncovered. Most of these are conserved in eukaryotes, but important differences between species exist. Here we review current concepts of mitotic checkpoint activation and silencing. Guided by studies in model organisms and our phylogenomics analysis of checkpoint constituents and their functional domains and motifs, we highlight ancient and taxa-specific aspects of the core checkpoint modules in the context of mitotic checkpoint function.
Insights
The mitotic checkpoint prevents errors in cell division by ensuring proper chromosome attachment. This review highlights conserved and species-specific mechanisms of its activation and silencing.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- The mitotic checkpoint is crucial for preventing aneuploidy by delaying cell division until all chromosomes are correctly attached to the spindle.
- Fundamental principles of mitotic checkpoint activation and inactivation are largely understood but exhibit species-specific variations.
- Understanding these variations is key to comprehending cell cycle regulation across eukaryotes.
Purpose of the Study:
- To review current concepts of mitotic checkpoint activation and silencing.
- To highlight conserved and taxa-specific aspects of core mitotic checkpoint modules.
- To provide insights into the evolution and functional diversity of the mitotic checkpoint.
Main Methods:
- Literature review of current concepts in mitotic checkpoint regulation.
- Phylogenomics analysis of checkpoint protein constituents, domains, and motifs.
- Comparative analysis of checkpoint mechanisms across model organisms.
Main Results:
- Identified conserved molecular principles underlying mitotic checkpoint function.
- Highlighted significant differences in checkpoint activation and silencing mechanisms across eukaryotic taxa.
- Detailed ancient and species-specific features of core checkpoint modules.
Conclusions:
- The mitotic checkpoint exhibits both conserved and divergent evolutionary paths.
- Species-specific adaptations in checkpoint components contribute to functional diversity.
- Further research into these variations can illuminate fundamental aspects of cell division control.
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