REPRESSION OF GROWTH-REGULATED G1 CYCLIN EXPRESSION BY CYCLIC-AMP IN BUDDING YEAST

YEAST cell becomes committed to the cell division cycle only if it grows to a critical size(1-4) and reaches a critical rate of protein synthesis(5,6). The coordination between growth and division takes place at a control step during the G1 phase of the cell cycle called Start(4). It relies on the G1-specific cyclins encoded by CLN1, 2 and 3, which trigger Start through the activation of the Cdc28 protein kinase. In fact, the Cln cyclins are rate-limiting for Start execution and depend on growth. Here we report that the cyclic AMP signal pathway(11) modulates the dependency of Cln cyclins on growth. In particular, more growth is required to trigger Start because CLN1 and CLN2 are repressed by the cAMP signal, thus explaining the previously observed cAMP-dependent increase of the critical size and critical rate of protein synthesis(12). Cln3 is not inhibited by the cAMP pathway and counteracts this mechanism by partially mediating the growth-dependent expression of other G1 cyclins.