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Novel Insights into the Multifaceted Mitotic Kinases

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Mitosis refers to the complex yet elegant stage of the cell cycle during which a cell divides its genetic material to each of the nascent daughter cells. Conceptually, mitosis itself can be envisioned as a mini circuit with separate but sequential steps, each with a defined set of tasks that must be completed ...

Mitosis refers to the complex yet elegant stage of the cell cycle during which a cell divides its genetic material to each of the nascent daughter cells. Conceptually, mitosis itself can be envisioned as a mini circuit with separate but sequential steps, each with a defined set of tasks that must be completed in a timely manner and with great fidelity in order to ensure equal division of the genome and hence successful survival of progeny. It is clear now that the driving force of mitosis is a wave of tightly regulated and coordinated events orchestrated by a panel of kinases, and their counteracting phosphatases. These structurally and functionally diverse kinases are collectively known as the mitotic kinases, in recognition of their critical role in ensuring the accurate completion of genome and cell division.

Mitosis begins with prophase during which cyclin-dependent kinase-1 (CDK1)-driven DNA condensation is initiated and, in vertebrates, loss of cohesion between the duplicated chromosomes begins in response to phosphorylation by polo-like-kinase 1 (PLK1) and Aurora B. During prometaphase, the coordinated activity of Aurora A, NEK family kinases and PLK1 amongst others promotes centrosome maturation and formation of a dynamic bipolar mitotic spindle. Construction of the kinetochore, a large multimolecular complex that assembles onto centromeres and forms the primary interaction site of spindle microtubule is dependent on multiple inputs including those from CDK1, PLK1, Haspin and Aurora B. The activity of the Spindle Assembly Checkpoint (SAC), a signaling pathway that monitors the interaction between spindle microtubules and the chromatid pair is at its maximum during prometaphase. The activity of the SAC is driven by yet another kinase cascade starting with the monopolar spindle 1 kinase (MPS1) which recruits the Budding Uninhibited by Benzimidazole 1 (BUB1) kinase and its pseudokinase paralog BUB1-related 1 (BUBR1) to kinetochores with additional contribution of Haspin and Aurora B kinases. Alignment of sister chromatid pairs to the spindle equator and termination of the SAC signals metaphase end and, at the molecular level, is thought to initiate a phosphatase relay that reverses phosphorylation generated by the mitotic kinases.

In this Research Topic, we propose to create an interactive forum for reporting and discussing recent progress that pertain to the regulation and function of the mitotic kinases. We encourage submission of hypothesis and theory articles as well as reviews. We particularly favour discussion of crosstalk and cross-regulation between mitotic kinases and between the kinases and their counteracting phosphatases, discussion on mitotic kinase function throughout evolution and in exotic model organisms, and alternative cellular divisions (endomitosis, meiosis), as well as new structural and mechanistic insights into kinase regulation and activation.


Keywords: mitosis, spindle, spindle checkpoint, kinase, phosphatase, kinetochore, centromere, centrosome


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