P25(RUM1) ORDERS S-PHASE AND MITOSIS BY ACTING AS AN INHIBITOR OF THEP34(CDC2) MITOTIC KINASE

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