43rd ANNUAL DROSOPHILA RESEARCH CONFERENCE
April 10-14, 2002

PROGRAM AND ABSTRACT VOLUME
Workshop Abstract

28W
The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time. Jordan Raff, Kim Jeffers, Jun-yong Huang. Wellcome/CRC Institute, Tennis Court Road, Cambridge CB2 1QR, UK.

In Drosophila cells cyclin B is degraded in two phases. Destruction of the spindle-associated cyclin B initiates at centrosomes and spreads to the spindle equator; any remaining cytoplasmic cyclin B is then degraded slightly later in mitosis. We show that the APC/C regulators Fzy/Cdc20 and Fzr/Cdh1 bind to microtubules in embryo extracts. Fzy is concentrated at kinetochores and centrosomes, while Fzr is concentrated at centrosomes. In syncytial embryos, only Fzy is present and this catalyses only the first phase of cyclin B destruction on the mitotic spindle. In cellularised embryos, both Fzy and Fzr are present, and we show that Fzr can catalyse the destruction of cyclin B both on the spindle and in the cytoplasm. We propose that the activation of Fzy normally triggers the first phase of cyclin B destruction on the mitotic spindle. This then activates Fzr, which triggers the second phase of cyclin B destruction throughout the cell. The concentration of Fzy and Fzr at centrosomes may enhance the fidelity of this sequential activation, and probably explains why the destruction of cyclin B appears to initiate at centrosomes. These observations may have important implications for the mechanisms of the spindle checkpoint.