A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

Balestra, Aurélia C; Zeeshan, Mohammad; Rea, Edward; Pasquarello, Carla; Brusini, Lorenzo; Mourier, Tobias; Subudhi, Amit Kumar; Klages, Natacha; Arboit, Patrizia; Pandey, Rajan; Brady, Declan; Vaughan, Sue; Holder, Anthony A; Pain, Arnab; Ferguson, David JP; Hainard, Alexandre; Tewari, Rita; Brochet, Mathieu

Cell 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. 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 divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication.