Legendary Kinase Controls Early Mitoses

Abstract

Chinese legend has it that Pan Gu broke out of an egg, created the heavens and earth out of chaos (and egg parts), and stood on the earth to hold up the heavens. At the end of the Western 20th century, Pan Gu has been reborn as a serine-threonine kinase. The DNA replication block that follows meiosis is derepressed at fertilization, but just how the unfertilized ovum is prevented from entering S phase is largely a mystery. Fenger et al. have identified and characterized Pan Gu (PNG), which controls the onset of embryonic DNA synthesis in Drosophila . png is expressed only in the maternal ovaries and in embryos up to 3 hours after fertilization. Because plutonium ( plu ) mutants can enhance the phenotype evinced by weak png mutations (aberrant DNA synthesis and mitoses), the authors asked whether PNG and PLU (an ankyrin-repeat protein) associate. PNG immunoprecipitated with PLU; however, association was dependent on PNG kinase activity, suggesting that phosphorylation or the wild-type conformation of PNG was essential for coprecipitation. Additionally, association of PNG and PLU appeared indirect and was most likely mediated by an unknown adaptor protein, as PNG and PLU failed to associate in yeast two-hybrid experiments. PNG stabilized the levels of cyclin A and B, and led to higher levels of histone phosphorylation, presumably mediated by the kinase CDC2. These results suggest a mechanism whereby S phase is suppressed: by keeping mitotic kinases active (which prevent the activation of DNA replication origins), and maintaining chromatin in a highly condensed state (through histone phosphorylation), PNG may control the switch from mitosis to DNA synthesis in early Drosophila embryos. Fenger, D.D., Carminati, J.L., Burney-Sigman, D.L., Kashevsky, H., Dines, J.L., Elfring, L.K., and Orr-Weaver, T.L. (2000). PAN GU: A protein kinase that inhibits S phase and promotes mitosis in early Drosophila development. Development 127 : 4763-4774. [Online Journal]