DOMINANT MUTANTS IDENTIFY NEW ROLES FOR P34(CDC2) IN MITOSIS

A large number of dominant mutants have been generated in the fission yeast cdc2 gene, causing lethality when expressed in wild-type cells, The mutants interfere with distinct aspects of p34(cdc2) function, pro ducing one of four different phenotypes: mitotic arrest, multiple roun ds of S phase in the absence of mitosis, premature mitosis or G(2) arr est, The mitotic mutants DL41, DL45 and DL50 are characterized in this paper, Over-expression of DL41 or DL45 causes mitotic arrest, specifi cally interfering with sister chromatid separation, without preventing spindle elongation, This suggests a role for p34(cdc2) in triggering sister chromatid separation at anaphase, DL41 and DL45 also cause abno rmal septum formation, suggesting that p34(cdc2) may also be involved in regulating this process in fission yeast, These mitotic aspects of p34(cdc2) function may involve interaction with p13(suc1), since incre ased expression of suc1 partially suppresses DL41 and DL45. Over-expre ssion of DL50 causes premature mitotic entry in cells that have not co mpleted S phase, resulting in lethality, DL41, DL45 and DL50 correspon d to mutation of p34(cdc2) residues predicted to be on the surface of the protein, identifying potential sites of interaction with mitotic r egulators of p33(cdc2), and these residues are conserved amongst cdc2 proteins found in other eukaryotes.