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

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 interdepende...

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Published inbioRxiv
Main Authors Balestra, Aurelia C, Zeeshan, Mohammad, Rea, Edward, Pasquarello, Carla, Brusini, Lorenzo Alfredo, Mourier, Tobias, Subudhi, Amit Kumar, Arboit, Patrizia, Klages, Natacha, Pandey, Rajan, Brady, Declan, Vaughan, Sue, Holder, Anthony A, Pain, Arnab, Ferguson, David, Hainard, Alexandre, Tewari, Rita, Brochet, Mathieu
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.06.2020
Subjects
Cell cycle
Cyclin-dependent kinase
Cyclin-dependent kinases
Cyclins
Deoxyribonucleic acid
DNA
DNA biosynthesis
Life cycles
Malaria
Mitosis
Plasmodium
Plasmodium berghei
Replication
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Summary: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. 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.02.14.928432