A collaborative study between the Hochegger (Sussex), Novak (Oxford) and Ly groups investigated the specialised functions of two mitotic cyclin types, cyclin A and B. Authors Image Using rapid inducible protein removal, we analyse how acute depletion of these proteins affects mitosis. Loss of cyclin A in G2‐phase prevents mitotic entry. Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phosphatase inactivation by Greatwall kinase. Beyond this point, cyclin B/Cdk1 is essential for phosphorylation of a distinct subset of mitotic Cdk1 substrates that are essential to complete cell division. Hégarat, N., Crncec, A., Suarez Peredo Rodriguez, M.F., Echegaray Iturra, F., Gu, Y., Busby, O., Lang, P.F., Barr, A.R., Bakal, C., Kanemaki, M.T., Lamond, A.I., Novak, B., Ly, T., Hochegger, H. Summary of Paper by Lori Koch Cells divide by replicating their DNA in S phase and then segregating their chromosomes during mitosis. The distinct phases of the cell cycle are orchestrated by cyclin-dependent kinases (Cdks), which can associate with unique cyclin proteins to phosphorylate different groups of proteins in each phase. However, evidence suggests that some cyclins have overlapping expression patterns and functionality, making it difficult to discern precise requirements. In a recent study published in EMBO Journal, scientists from the Hochegger (Sussex), Novak (Oxford), and Ly (WCB) groups investigated the contributions of cyclins A and B in promoting cell cycle progression in human cells. Using a robust genetic system to inducibly degrade specific cyclins, they determined that lack of cyclin A2 delayed S phase progression and then arrested cells in G2. In contrast, degrading cyclins B1 and B2, either alone or together, did not prevent progression through S nor entry into mitosis but led to chromosome alignment and segregation defects during a prolonged mitosis phase. Next, the researchers found that in addition to cyclin B1-Cdk activity, low PP2A:B55 phosphatase activity was required for nuclear envelope breakdown during early mitosis. To identify cyclin B1-specific phosphorylation sites, group leader Tony Ly and colleagues performed phospho-proteomic analysis on samples from control and cyclin B1-depleted cells. They identified a group of phospho-sites, representing ~3.5% of the phospho-proteome and ~5.6% of all Cdk consensus sites, that were changed upon cyclin B1 depletion. Together, the results revealed that Cdk-cyclin B1 and PP2A:B55 phosphatase work together to promote major events in mitosis. Related links Journal Link Ly Lab Website DOI This article was published on 2024-06-17
