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

View ORCID ProfileAurélia C Balestra, View ORCID ProfileMohammad Zeeshan, View ORCID ProfileEdward Rea, Carla Pasquarello, View ORCID ProfileLorenzo Brusini, View ORCID ProfileTobias Mourier, View ORCID ProfileAmit Kumar Subudhi, Natacha Klages Jemelin, Patrizia Arboit, Rajan Pandey, View ORCID ProfileDeclan Brady, View ORCID ProfileSue Vaughan, View ORCID ProfileAnthony A Holder, View ORCID ProfileArnab Pain, View ORCID ProfileDavid J P Ferguson, Alexandre Hainard, View ORCID ProfileRita Tewari, View ORCID ProfileMathieu Brochet
doi: https://doi.org/10.1101/2020.02.14.928432
Aurélia C Balestra
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Mohammad Zeeshan
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Edward Rea
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Carla Pasquarello
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Lorenzo Brusini
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Tobias Mourier
3Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Kingdom of Saudi Arabia
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Amit Kumar Subudhi
3Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Kingdom of Saudi Arabia
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Natacha Klages Jemelin
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Patrizia Arboit
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Rajan Pandey
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Declan Brady
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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Sue Vaughan
4Oxford Brookes University, Department Biological & Medical Sciences, United Kingdom
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Anthony A Holder
5The Francis Crick Institute, Malaria Parasitology Laboratory, London, United Kingdom
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Arnab Pain
3Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Kingdom of Saudi Arabia
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David J P Ferguson
4Oxford Brookes University, Department Biological & Medical Sciences, United Kingdom
6University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Science, Oxford OX3 9DU, United Kingdom
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Alexandre Hainard
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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Rita Tewari
2University of Nottingham, School of Life Sciences, Nottingham, United Kingdom
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  • For correspondence: mathieu.brochet@unige.ch
Mathieu Brochet
1University of Geneva, Faculty of Medicine, Geneva, Switzerland
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  • For correspondence: mathieu.brochet@unige.ch
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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. 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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 07, 2020.
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A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission
Aurélia C Balestra, Mohammad Zeeshan, Edward Rea, Carla Pasquarello, Lorenzo Brusini, Tobias Mourier, Amit Kumar Subudhi, Natacha Klages Jemelin, Patrizia Arboit, Rajan Pandey, Declan Brady, Sue Vaughan, Anthony A Holder, Arnab Pain, David J P Ferguson, Alexandre Hainard, Rita Tewari, Mathieu Brochet
bioRxiv 2020.02.14.928432; doi: https://doi.org/10.1101/2020.02.14.928432
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A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission
Aurélia C Balestra, Mohammad Zeeshan, Edward Rea, Carla Pasquarello, Lorenzo Brusini, Tobias Mourier, Amit Kumar Subudhi, Natacha Klages Jemelin, Patrizia Arboit, Rajan Pandey, Declan Brady, Sue Vaughan, Anthony A Holder, Arnab Pain, David J P Ferguson, Alexandre Hainard, Rita Tewari, Mathieu Brochet
bioRxiv 2020.02.14.928432; doi: https://doi.org/10.1101/2020.02.14.928432

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