Journal
JOURNAL OF CELL BIOLOGY
Volume 154, Issue 1, Pages 85-94Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200102007
Keywords
cell cycle; cyclin-dependent kinases; mitosis; S phase; ubiquitin
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Funding
- NICHD NIH HHS [P30 HD27823-10, K08 HD01203] Funding Source: Medline
- NIGMS NIH HHS [R01 GM55772] Funding Source: Medline
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Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis is the inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was Proposed previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in a graded manner and is not extinguished until S phase. Complete inactivation of APC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activity throughout G1 helps to ensure the proper timing of Cdc20p expression. This suggests that S phase cyclins have an important role in allowing the accumulation of mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APC(Cdh1), and APC(Cdh1).
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