A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of Plasmodium berghei during gametogony and parasite transmission
Holder, Anthony A.
Ferguson, David J P
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/661753
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AbstractCell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission. It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. We also provide evidence for indirect regulation of the concomitant M-phase progression. During a replicative cycle, CRK5 stably interacts with a single Plasmodium-specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. Our results provide evidence that during Plasmodium male gametogony, this unique cyclin/CDK pair fills the functional space of multiple eukaryotic cell-cycle kinases controlling DNA replication and M-phase progression.
CitationBalestra, A., Zeeshan, M., Rea, E., Pasquarello, C., Klages, N., Mourier, T., … Brochet, M. (2020). A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of Plasmodium berghei during gametogony and parasite transmission. doi:10.1101/2020.02.14.928432
SponsorsWe thank Julie Rodger (Nottingham Universitiy) for her assistance in the insectary maintenance and Zineb Rchiad (KAUST) for RNAseq library preparation. We thank the excellent service at the bioimaging and flow-cytometry core facilities at the Faculty of Medicine of the University of Geneva. We also would like to thank Nisha Philip (University of Edinburgh) for sharing the 615 Tir1-expressing line as well as Wesley Van Voorhis and Kayode Ojo (University of Washington) for sharing compound BKI-1294. We thank Markus Ganter for sharing the reference GO term set used in this work.
PublisherCold Spring Harbor Laboratory