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.
Balestra, Aurélia C.Zeeshan, MohammadRea, EdwardPasquarello, CarlaBrusini, LorenzoMourier, TobiasSubudhi, Amit KumarKlages, NatachaArboit, PatriziaPandey, RajanBrady, DeclanVaughan, Sue
Holder, Anthony A.Pain, ArnabFerguson, David J.P.Hainard, AlexandreTewari, RitaBrochet, Mathieu
Department of Biological and Medical Sciences
Year of publication: 2020Date of RADAR deposit: 2022-05-17