Nayak et al. reveal that γ-tubulin, better known as a microtubule-nucleating protein, controls the cell cycle by switching off a key mitotic regulator during interphase.
Evidence suggests that γ-tubulin has microtubule-independent functions: a γ-tubulin mutant called mipAD159 causes mitotic defects in Aspergillus nidulans, even though the fungus continues to assemble mitotic spindles and interphase microtubule arrays. Aspergillus cells contain multiple nuclei, which pass through the cell cycle synchronously. But mipAD159 blocks some nuclei from entering mitosis, or causes problems with chromosome segregation and mitotic exit.
To investigate how cell cycle regulation is disrupted in mipAD159 fungi, Nayak et al. followed the localization of mitotic regulatory proteins over the course of the cell cycle in strains carrying the mutation. Cyclin B, cyclin-dependent kinase 1, and the phosphatase Cdc14 all failed to accumulate in some nuclei during interphase, preventing them from entering mitosis. Other nuclei in the same cell divided, but the fraction of stalled nuclei increased with every cycle until the fungus stopped growing.
Nayak et al. traced this failure in protein accumulation to the continuous activity of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets mitotic proteins for destruction to help nuclei exit mitosis. The APC/C is usually inactivated during interphase to allow initiation of DNA synthesis and accumulation of mitotic proteins that drive the next round of division. This failed in many nuclei in mipAD159 cells, but many of the paused nuclei could re-enter the cell cycle if the APC/C was switched off with a drug. Author Berl Oakley now wants to investigate how γ-tubulin inactivates the APC/C in wild-type cells.
