During its active period in G1, Cdh1 (green) localizes to the spindle pole bodies of an Aspergillus cell containing multiple nuclei (red).

During its active period in G1, Cdh1 (green) localizes to the spindle pole bodies of an Aspergillus cell containing multiple nuclei (red).

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.

References

References
Edgerton-Morgan
H.
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Oakley
B.R.
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2012
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J. Cell Biol.
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