Molecular Regulation of Mitosis and Its Role in Disease

Dear Colleagues,

Mitotic division involves a profound cellular reorganization essential for the precise repartition of the genome between daughter cells. The nuclear envelope is disassembled, the microtubule dynamics dramatically change to form the bipolar spindle and DNA is condensed into chromosomes. A protein complex in the centromeric region of the chromosomes is assembled to form the kinetochores, a structure that will function as a mechanical latch allowing their attachment to the spindle microtubules. The chromosomes are then precisely aligned on the metaphase plate, a mechanism that is under the control of the spindle assembly checkpoint (SAC). This surveillance signalling pathway is activated by unattached chromosomes and prevents the metaphase-to-anaphase transition by inhibiting the anaphase promoting complex (APC), the ubiquitin ligase responsible for securin and cyclin B degradation. Finally, once the SAC is satisfied, anaphase takes place, an event that is followed by spindle disorganization, the reformation of the nuclear envelope and cytokinesis yielding to two daughter cells.

All these events are driven by waves of protein phosphorylation/dephosphorylation resulting from the oscillation of the kinase/phosphatase activity balance. This balance swings from massive kinase activity and protein phosphorylation at the early stages of mitosis to high phosphatase activity and protein dephosphorylation upon anaphase onset.

In this special issue of Cells, the mechanisms driving coordinated mitosis and the different signalling networks generating accurate kinetochore-dependent chromosome segregation, SAC activation/inactivation and cytokinesis will be discussed. Moreover, particular attention will be paid to the mechanisms controlling and conferring the accurate protein phosphorylation/dephosphorylation balance required for mitosis and the pathological disorders deriving from errors in this major cellular event.

Dr. Thierry Lorca
Dr. Anna Castro
Guest Editors

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