Differential regulation of growth and checkpoint control mediated by a Cdc25 mitotic phosphatase from Pneumocystis carinii

Pneumocystis carinii is an opportunistic fungal pathogen phylogenetically r elated to the fission yeast Schizosaccharomyces pombe. P. carinii causes se vere pneumonia in immunocompromised patients with AIDS and malignancies. Al though the life cycle of P, carinii remains poorly characterized, morpholog ic studies of infected lung tissue indicate that P. carinii alternates betw een numerous small trophic forms and fewer large cystic forms. To understan d further the molecular mechanisms that regulate progression of the cell cy cle of P, carinii, we have sought to identify and characterize genes in P. carinii that are important regulators of eukaryotic cell cycle progression. In this study, we have isolated a cDNA from P. carinii that exhibits signi ficant homology, but unique functional characteristics, to the mitotic phos phatase Cdc25 found in S. pombe. P. carinii Cdc25 was shown to rescue growt h of the temperature-sensitive S. pombe cdc25-22 strain and thus provides a n additional tool to investigate the unique P.. carinii life cycle. Althoug h P. carinii Cdc25 could also restore the DNA damage checkpoint in cdc25-22 cells, it was unable to restore fully the DNA replication checkpoint. The dissociation of checkpoint control at the level of Cdc25 indicates that Cdc 25 may be under distinct regulatory control in mediating checkpoint signali ng.