Functional Distinction Between Cln1p and Cln2p Cyclins in the Control of the Saccharomyces cerevisiae Mitotic Cycle

Cln1p and Cln2p are considered as equivalent cyclins on the basis of sequence homology, regulation, and functional studies. Here we describe a functional distinction between the Cln1p and Cln2p cyclins in the control of the G1/S transition. Inactivation of CLN2, but not of CLN1, leads to a larger-than-normal cell size, whereas overexpression of CLN2, but not of CLN1, results in smaller-than-normal cells. Furthermore, mild ectopic expression of CLN2, but not of CLN1, suppresses the lethality of swi4swi6 and cdc28 mutant strains. In the absence of Cln1p, the kinetics of budding, initiation of DNA replication, and activation of the Start-transcription program are not affected; by contrast, loss of Cln2p causes a delay in bud emergence. A primary role for Cln2p but not for Cln1p in budding is reinforced by the observation that only the cln2 mutation is synthetic lethal with a cdc42 mutation, and only the cln2 mutant strain is hypersensitive to latrunculin B. In addition, we found that Cln1p showed a more prominent nuclear staining than Cln2p. Finally, chimeric proteins composed of Cln1p and Cln2p revealed that Cln2p integrity is required for its functional specificity.