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

Abstract

© 2020, Balestra et al. 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.

Citation

Balestra, A. C., Zeeshan, M., Rea, E., Pasquarello, C., Brusini, L., Mourier, T., Subudhi, A. K., Klages, N., Arboit, P., Pandey, R., Brady, D., Vaughan, S., Holder, A. A., Pain, A., Ferguson, D. J., Hainard, A., Tewari, R., & Brochet, M. (2020). A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission. eLife, 9, Article e56474. https://doi.org/10.7554/eLife.56474

• Journal Article Type: Article
• Acceptance Date: Jun 8, 2020
• Online Publication Date: Jun 22, 2020
• Publication Date: Jun 22, 2020
• Deposit Date: Jun 25, 2020
• Publicly Available Date: Jun 25, 2020
• Journal: eLife
• Electronic ISSN: 2050-084X
• Publisher: eLife Sciences Publications
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Article Number: e56474
• DOI: https://doi.org/10.7554/eLife.56474
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Immunology and Microbiology; General Neuroscience; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4709177
• Publisher URL: https://elifesciences.org/articles/56474