| Budding yeast phosphoinositide-specific phospholipase C (Plc1p) is the enzyme responsible for the metabolism of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] into the secondary messengers inositol 1,4,5-trisphosphate [IP3] and 1,2-diacylglycerol [DAG]. Current research supports a more global regulatory function for Plc1p than previously believed. Our lab recently established that Plc1p localizes to and interacts with kinetochore proteins for efficient chromosome segregation (Lin et al., 2000). Furthermore, plc1Delta cells are nocodazole sensitive, a common phenotype of spindle checkpoint mutants.;Although multiple assays revealed that Plc1p is not a spindle checkpoint component, deletion of PLC1 activates the spindle checkpoint pathway. Consequently, plc1Deltabub1Delta and plc1Deltabub3Delta strains displayed a viability decrease and growth defects. Genetic interactions were also observed between plc1Delta and multiple kinetochore components.;We used the nocodazole sensitivity phenotype of plc1Delta and screened for extragenic suppressors. This search identified SIN4 , a mediator complex component of RNA polymerase II. The mediator complex regulates transcription by interacting with multiple chromatin remodeling factors. Consequently, this suppression encouraged an examination of additional interactions between the PLC1 and other transcription components.;Remarkably, plc1Delta was synthetic lethal with several components of the SAGA complex, ssn6Delta, which encodes a component of the Tup1p/Ssn6p global corepressor complex, and swi6Delta , which encodes a component of two separate transcription complexes.;We also explored the genetic interactions of ipk2Delta and ipk1Delta to all of the genes mentioned above which were synthetic lethal or displayed growth defects with plc1Delta . IPK2 encodes Ipk2p, which catalyzes the metabolism of inositol trisphosphate (IP3) to inositol tetrakisphosphate (IP 4) and inositol pentakisphosphate (IP5), and IPK1 encodes Ipk1p, which catalyzes the metabolism of IP5 to inositol hexakisphosphate (IP6). Only ipk2Delta was synthetic lethal with three genes: gcn5Delta, swi6Delta, and spt7Delta, indicating the synthesis of IP3 is more critical than IP4, IP5 or IP6 for the function of transcription regulatory complexes.;Collectively, the data support a regulatory role for Plc1p through the regulation of chromatin remodeling complexes, and multiple phenotypes and interactions of Plc1p may be explained via altered chromatin conformation. |
