Edgerton-Morgan and Oakley reveal that γ-tubulin promotes cells’ entry into S phase by controlling the localization of a key cell cycle regulator.
γ-Tubulin is best known for nucleating microtubules at microtubule-organizing centers such as centrosomes or fungal spindle pole bodies, but γ-tubulin also regulates the cell cycle. Aspergillus nidulans strains expressing the γ-tubulin mutant mipA-D159 fail to inactivate a ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C) during interphase. This prevents the accumulation of proteins such as cyclin B and cyclin-dependent kinase 1 that would normally initiate DNA synthesis and cell cycle progression.
In many species, a protein called Cdh1 activates the APC/C during G1 to prevent premature entry into S phase. Edgerton-Morgan and Oakley found that Aspergillus Cdh1 delays S phase by targeting cyclin B for destruction and that mipA-D159 strains lacking Cdh1 were once more able to accumulate cyclin B and progress through the cell cycle. Cdh1 localized to spindle pole bodies while it was active in G1 but disappeared as the cells entered S phase. In mipA-D159 mutants, however, Cdh1 remained at the spindle pole bodies for longer, suggesting that γ-tubulin normally inactivates the APC/C by promoting Cdh1’s displacement from these structures.
Senior author Berl Oakley now wants to investigate how γ-tubulin regulates Cdh1’s localization and to understand why this is compromised in mipA-D159 mutants. The most likely explanation, Oakley says, is that wild-type γ-tubulin binds to a protein that promotes Cdh1’s destruction or dissociation from the spindle pole body.