TheFission Yeastdis3+GeneEncodes a 11O-kDa Essential Protein Implicated inMitotic Control

Thefission yeastmutantdis3-54 isdefective inmitosis andfails inchromosome disjunction. Itsphenotype is similar tothatofdis2-11, amutantwith amutation inthetype1protein phosphatase gene.We cloned thedis3+ genebytransformation. Nucleotide sequencing predicts a coding region of970amino acids interrupted bya 164-bp intron atthe65thcodon. Thepredicted dis3+ protein shares a weakbutsignificant similarity withthe budding yeast SSDIor SRKIgeneproduct, thegeneforwhichisa suppressorfortheabsence ofa protein phosphatase SIT4gene or theBCYIregulatory subunit ofcyclicAMP-dependent protein kinase. Anti-dis3 antibodies recognized the110-kDa dis3+ geneproduct, whichispartofa 250-to350-kDaoligomer andis enriched inthenucleus. Thecellular localization ofthedis3+ protein isreminiscent ofthatofthedis2+ protein, butthese twoproteins donotforma complex. A type1protein phosphatase activity inthedis3-54 mutant extracts isapparently notaffected. Thedis3+ geneisessential forgrowth; genedisruptant cells donot germinate andfail incelldivision. Increased dis3+ genedosage reversestheTs'phenotype ofa cdc25wee) strain, asdoesincreased type1protein phosphatase genedosage. Double mutantdis3 dis2islethal evenatthe permissive temperature, suggesting thatthedis2+anddis3+ genesmay befunctionally overlapped. Therole ofthedis3+ geneproduct inmitosis isunknown, butthis geneproduct may bedirectly or indirectly involved intheregulation ofmitosis. Protein phosphorylation anddephosphorylation areimportant posttranslational modifications essential for avariety ofbiological systems. Inmitotic cell cycle control, cdc2+ protein kinaseplays a pivotal roleas a componentof maturation/M-phase promoting factor (21); itsphosphorylation statechanges during thecell cycle, anditsactivity is regulated bydephosphorylation (9). Incontrast totheiden