The role of Cak1 in promoting pre-meiotic S-phase.
Karen Schindler (1), Kirsten R. Benjamin (2), Andrew Boglioli
(1), Edward Winter (1)
(1) Department of Biochemistry, Thomas Jefferson University, 233 S. 10th
St., Philadelphia, PA 19107, USA;
(2) Department of Biochemistry and Biophysics, University of California,
San Francisco, CA 94143, USA
CAK1 encodes a protein kinase whose sole essential role during
mitosis is to activate the cyclin dependent kinase, Cdc28. While mitosis
and meiosis share many regulatory mechanisms that promote progression of
key cell cycle events, differences do exist in order to control the
specialized process of haploidization. Cak1 activates Cdc28 in meiosis
as it does in mitosis. However, it also functions in a Cdc28-independent
fashion at multiple steps in sporulation (Schaber et al. MCB
2002, Wagner et al. EMBO 1997). The earliest function is required
to initiate pre-meiotic S-phase, while a later function activates the
Smk1 MAP kinase pathway that controls spore formation. In this study, we
have generated a series of mutants to investigate Cak1's early role.
Analyses of these mutants show that Cak1 regulates S-phase by promoting
the destruction of the cyclin dependent kinase inhibitor, Sic1. Cak1
also promotes DNA replication through a Sic1-independent mechanism.
Moreover, Cak1 is required to activate the Ime2 protein kinase. Our
observations suggest that Cak1 positively regulates Ime2 which in turn
promotes S-phase through activating Sic1 destruction.
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