MYB-RELATED SCHIZOSACCHAROMYCES-POMBE CDC5P IS STRUCTURALLY AND FUNCTIONALLY CONSERVED IN EUKARYOTES

Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essen tial for G(2)/M progression. To explore the structural and functional conservation of Cdc5 throughout evolution, we isolated Cdc5-retated ge nes and cDNAs from Saccharomyces cerevisiae, Caenorhabditis elegans, D rosophila melanogaster; and Homo sapiens. Supporting the notion that t hese Cdc5 gene family members are functionally homologous to S. pombe cdc5(+), human and fly Cdc5 cDNAs are capable of complementing the tem perature-sensitive lethality of the S. pombe cdc5-120 mutant. Furtherm ore, S. cerevisiae CEF1 (S. cerevisiae homolog of cdc5+), like S. pomp e cdc5(+), is essential during G(2)/M. The location of the cdc5-120 mu tation, as well as mutational analyses of Cef1p, indicate that the Myb repeats of cddp and Cef1p are important for their function in vivo. H owever, we Sound that unlike in c-Myb; single residue substitutions of glycines for hydrophobic residues within the Myb repeats of Cef1p, wh ich are essential for maintaining structure of the Myb domain, did not impair Cef1p function in vivo. Rather, multiple W-to-G substitutions were required to inactivate Cef1p, and many of the substitution mutant s were found to confer temperature sensitivity; Although it is possibl e that Cef1p acts as a transcriptional activator, we have demonstrated that Cef1p is not involved in transcriptional activation of a class o f G(2)/M-regulated genes typified by SWI5. Collectively, these results suggest that Cdc5 family members participate in a novel pathway to re gulate G(2)/M progression.