CDC44 - A PUTATIVE NUCLEOTIDE-BINDING PROTEIN REQUIRED FOR CELL-CYCLEPROGRESSION THAT HAS HOMOLOGY TO SUBUNITS OF REPLICATION FACTOR-C

To investigate the means by which a cell regulates the progression of the mitotic cell cycle, we characterized cdc44, a mutation that causes Saccharomyces cerevisiae cells to arrest before mitosis. CDC44 encode s a 96-kDa basic protein with significant homology to a human protein that binds DNA (PO-GA) and to three subunits of human replication fact or C (also called activator 1). The hypothesis that Cdc44p is involved in DNA metabolism is supported by the observations that (i) levels of mitotic recombination suggest elevated rates of DNA damage in cdc44 m utants and (ii) the cell cycle arrest observed in cdc44 mutants is all eviated by the DNA damage checkpoint mutations rad9, mec1, and mec2. T he predicted amino acid sequence of Cdc44p contains GTPase consensus s ites, and mutations in these regions cause a conditional cell cycle ar rest. Taken together, these observations suggest that the essential CD C44 gene may encode the large subunit of yeast replication factor C.