AN INHIBITOR OF YEAST CYCLIN-DEPENDENT PROTEIN-KINASE PLAYS AN IMPORTANT ROLE IN ENSURING THE GENOMIC INTEGRITY OF DAUGHTER CELLS

The gene encoding a 40-kDa protein, previously studied as a substrate and inhibitor of the yeast cyclin-dependent protein kinase, Cdc28, has been cloned. The DNA sequence reveals that p40 is a highly charged protein of 32,187 Da with no significant homology to other proteins. Overexpression of the gene encoding p40, SIC1, produces cells with an elongated bud morphology similar to that of cells with depleted levels of the CLB gene products, suggesting that p40 acts as an inhibitor of Cdc28-Clb complexes in vivo. A SIC1 deletion is viable and has highly increased frequencies of broken and lost chromosomes. The deletion strain segregates out many dead cells that are primarily arrested at the G(2) checkpoint in an asymmetric fashion. Only daughters and young mothers display the lethal defect, while experienced mothers appear to grow normally. These results suggest that negative regulation of Cdc28 protein kinase activity by p40 is important for faithful segregation of chromosomes to daughter cells.