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

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posted on 10.11.2020, 09:48 by Aurélia C Balestra, Mohammad Zeeshan, Edward Rea, Carla Pasquarello, Lorenzo Brusini, Tobias Mourier, Amit Kumar Subudhi, Natacha Klages, Patrizia Arboit, Rajan Pandey, Declan Brady, Sue Vaughan, Anthony A Holder, Arnab Pain, David JP Ferguson, Alexandre Hainard, Rita Tewari, Mathieu Brochet
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.

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