The cdc19(+) gene encodes an essential member of the MCM family of rep
lication proteins in Schizosaccharomyces pombe. We have examined the s
tructure and function of the Cdc19p protein using molecular and geneti
c approaches. We find that overproduction of wild-type Cdc19p in wild-
type cells has no effect, but cdc19-P1 mutant cells do not tolerate el
evated levels of other MCM proteins or overexpression of mutant forms
of Cdc19p. We have found genetic interactions between cdc19(+) and gen
es encoding subunits of DNA polymerase delta and the replication initi
ator cdc18(+). We have constructed a series of point mutations and seq
uence deletions throughout Cdc19p, which allow us to distinguish essen
tial from nonessential regions of the protein. Not surprisingly, conse
rved residues in the MCM homology domain are required for protein func
tion, but some residues outside the core homology domain are dispensab
le.