This proposal concerns the biochemical mechanisms regulated by the anaphase promoting complex (APC) and the role of protein degradation, mediated by APC from metaphase through the G1 of the next cell cycle. These mechanisms are central to our understanding of the fidelity of chromosome segregation and thus are important for understanding pathologies, such as cancer. As the regulatory machinery for the cell cycle becomes better characterized in all organisms, there is an increased urgency and opportunity to connect this regulatory machinery to the events that characterize the cell cycle, such as chromosome replication and segregation, cytokinesis, and decisions concerning differentiation and proliferation. Here we examine the detailed mechanisms of chromosome segregation and in particular the role of two proteins, securin and separin, which act downstream of APC. We ask how these function to carry out chromosome separation and how fidelity control mechanisms intervene. We also ask what other processes are controlled by APC during mitosis and G1 by examining the function of two recently identified substrates. We ask how APC recognizes substrates and temporally distinguishes among them. Finally we examine the diversity of APC regulators and begin to characterize the possible role of APC outside the cell cycle.
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