The Biochemistry of Mitosis

Abstract

In this article, we will discuss the biochemistry of mitosis in eukaryotic cells. We will focus on conserved principles that, importantly, are adapted to the biology of the organism. It is vital to bear in mind that the structural requirements for division in a rapidly dividing syncytial Drosophila embryo, for example, are markedly different from those in a unicellular yeast cell. Nevertheless, division in both systems is driven by conserved modules of antagonistic protein kinases and phosphatases, underpinned by ubiquitin-mediated proteolysis, which create molecular switches to drive each stage of division forward. These conserved control modules combine with the self-organizing properties of the subcellular architecture to meet the specific needs of the cell. Our discussion will draw on discoveries in several model systems that have been important in the long history of research on mitosis, and we will try to point out those principles that appear to apply to all cells, compared with those in which the biochemistry has been specifically adapted in a particular organism.

Cyclin CYB-3 controls both S-phase and mitosis and is asymmetrically distributed in the early C. elegans embryo

“…Upon formation of Cdk1-cyclin B complexes, the catalytic Cdk1 subunit is phosphorylated and inhibited by Wee1/Myt1 (Wieser and Pines, 2015). Indeed, it is Wee1/Myt1-mediated phosphorylation of Cdk1 that is reinforced by the replication checkpoint during S-phase so that mitosis always follows a complete round of DNA replication (Wieser and Pines, 2015).…”

“…In metazoans, SPFs are typically composed of Cdk2 bound to either cyclins E or A, while MPFs are Cdk1 bound to Aand B-type cyclins (reviewed by Fisher, 2011;Siddiqui et al, 2013;Wieser and Pines, 2015). In some embryonic systems, however, it might be the case that both SPF and MPF contain Cdk1 (Farrell et al, 2012), and Cdk1 can perform both functions in mammalian cells that have lost Cdk2 (Ortega et al, 2003).…”

“…Indeed, it is Wee1/Myt1-mediated phosphorylation of Cdk1 that is reinforced by the replication checkpoint during S-phase so that mitosis always follows a complete round of DNA replication (Wieser and Pines, 2015). I used RNAi to deplete the Myt1 ortholog wee-1.3.…”

“…For this analysis it was also important to detect P-CDK-1, which is the tyrosine 15-phosphorylated and inhibited form of the enzyme. Tyrosine phosphorylation of Cdk-cyclin B complexes is required during S-phase to restrain mitotic entry until replication has finished (Wieser and Pines, 2015). I used a commercially available antibody raised against human P-CDK-1 for this analysis.…”

WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity

“…T he eukaryotic cell cycle is controlled by oscillations in the activities of key regulatory proteins through the interplay of reversible protein phosphorylation and irreversible ubiquitindependent proteolysis (1)(2)(3). By ubiquitinating essential cell-cycle proteins, the anaphase-promoting complex/cyclosome (APC/C) is the crucial RING E3 ubiquitin ligase that controls accurate sister chromatid segregation, cytokinesis, and the initiation of chromosome replication (4)(5)(6)(7)(8)(9).…”