A divergent cyclin/cyclin-dependent kinase complex controls progression through the atypical replicative cycles during Plasmodium berghei gametogony

ABSTRACT: Cell-cycle transitions are generally triggered by variations in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have evolved unique cell-cycles with a repertoire of ancestral CDKs and cyclins whose functions and interdependency remain elusive. Here, we show that the divergent Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical cell-cycle regulator of gametogony required for transmission to the mosquito. It phosphorylates canonical CDK motifs on components of the pre-replicative complex and is essential for DNA replication. We also provide evidence for indirect regulation of the concomitant progression through M-phase. Over a replicative cycle, CRK5 stably interacts with a single Plasmodium-specific cyclin (SOC2) with no evidence of SOC2 cycling through transcription, translation nor degradation. Our results present evidence that during Plasmodium gametogony, a unique and divergent cyclin/CDK pair evolved to fulfil the functional space of multiple eukaryotic cell-cycle kinases controlling S-phase entry and progression through M-phase.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Plasmodium Berghei Anka

TISSUE(S): Gametocyte

SUBMITTER: alexandre Hainard  

LAB HEAD: Mathieu Brochet

PROVIDER: PXD017308 | Pride | 2020-02-25

REPOSITORIES: Pride