A checkpoint roadmap for the complex cell division of Apicomplexa parasites

摘要: The unusual cell cycles of Apicomplexa parasites are remarkably flexible with the ability to complete cytokinesis and karyokinesis coordinately or postpone for several rounds chromosome replication well recognized. Despite this surprising biology, molecular machinery required achieve flexibility is largely unknown. In study, we provide comprehensive experimental evidence that apicomplexan utilize multiple Cdk-related kinases (Crks) coordinate division. We determined Toxoplasma gondii encodes seven atypical P-, H-, Y- L- type cyclins ten Crks regulate cellular processes. generated analyzed conditional tet-OFF mutants TgCrks four TgCyclins expressed in tachyzoite stage. These experiments demonstrated TgCrk1, TgCrk2, TgCrk4 TgCrk6, were essential growth revealing a remarkable number Crk factors necessary parasite replication. G1 phase arrest resulted from loss cytoplasmic TgCrk2 interacted P-type cyclin demonstrating an mechanism controls half T. cycle. showed employs at least three mitosis. Novel kinases, TgCrk6 spindle function centrosome duplication, respectively, while TgCrk1 its partner TgCycL daughter bud assembly. Intriguingly, mitotic did not interact any tested instead dynamically during mitosis indicating they may require timing mechanism. Altogether, our findings demonstrate distinctive complex mechanisms their novel replicative cycles.