Activity of the APC Cdh1 form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p

Abstract

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 Cdc20.