CLB5 AND CLB6, A NEW PAIR OF B-CYCLINS INVOLVED IN DNA-REPLICATION INSACCHAROMYCES-CEREVISIAE

The functions of the Cdc28 protein kinase in DNA replication and mitos is in Saccharomyces cerevisiae are thought to be determined by the typ e of cyclin subunit with which it is associated. G1-specific cyclins e ncoded by CLN1, CLN2, and CLN3 are required for entry into the cell cy cle (Start) and thereby for S phase, whereas G2-specific B-type cyclin s encoded by CLB1, CLB2, CLB3, and CLB4 are required for mitosis. We d escribe a new family of B-type cyclin genes, CLB5 and CLB6, whose tran scripts appear in late G1 along with those of CLN1, CLN2, and many gen es required for DNA replication. Deletion of CLB6 has little or no eff ect, but deletion of CLB5 greatly extends S phase, and deleting both g enes prevents the timely initiation of DNA replication. Transcription of CLB5 and CLB6 is normally dependent on Cln activity, but ectopic CL B5 expression allows cells to proliferate in the absence of Cln cyclin s. Thus, the kinase activity associated with Clb5/6 and not with Cln c yclins may be responsible for S-phase entry. Clb5 also has a function, along with Clb3 and Clb4, in the formation of mitotic spindles. Our o bservation that CLB5 is involved in the initiation of both S phase and mitosis suggests that a single primordial B-type cyclin might have be en sufficient for regulating the cell cycle of the common ancestor of many, if not all, eukaryotes.