P25(RUM1) ORDERS S-PHASE AND MITOSIS BY ACTING AS AN INHIBITOR OF THE P34(CDC2) MITOTIC KINASE

p25(rum1) from the fission yeast S. pombe is shown to act as a specific in vitro inhibitor of the p34(cdc2)/p56(cdc13) mitotic kinase. It is also shown that early G1 cells contain p25(rum1), which associates with and inhibits the mitotic kinase, and maintains p56(cdc13) miotic B cyclin at a low level, ensuring that these cells do not undergo a premature lethal entry into mitosis. A high level of p25(rum1) in G2 cells inhibits the p34(cdc2)/p56(cdc13) kinase that removes the block preventing a further S phase and leads to repeated rounds of DNA replication. Thus, the cyclin-dependent kinase inhibitor p25(rum1), acting on the p34(cdc2) mitotic kinase, plays an important role in ensuring the correct sequence of S phase and mitosis during the cell cycle.