Depletion of the mini-chromosome maintenance complex binding protein allows the progression of cytokinesis despite abnormal karyokinesis during the asexual development of Plasmodium falciparum

Cell Microbiol. 2021 Mar;23(3):e13284. doi: 10.1111/cmi.13284. Epub 2020 Nov 18.


The eukaryotic cell cycle is typically divided into distinct phases with cytokinesis immediately following mitosis. To ensure proper cell division, each phase is tightly coordinated via feedback controls named checkpoints. During its asexual replication cycle, the malaria parasite Plasmodium falciparum undergoes multiple asynchronous rounds of mitosis with segregation of uncondensed chromosomes followed by nuclear division with intact nuclear envelope. The multi-nucleated schizont is then subjected to a single round of cytokinesis that produces dozens of daughter cells called merozoites. To date, no cell cycle checkpoints have been identified that regulate the Plasmodium spp. mode of division. Here, we identify the Plasmodium homologue of the Mini-Chromosome Maintenance Complex Binding Protein (PfMCMBP), which co-purified with the Mini-Chromosome Maintenance (MCM) complex, a replicative helicase required for genomic DNA replication. By conditionally depleting PfMCMBP, we disrupt nuclear morphology and parasite proliferation without causing a block in DNA replication. By immunofluorescence microscopy, we show that PfMCMBP depletion promotes the formation of mitotic spindle microtubules with extensions to more than one DNA focus and abnormal centrin distribution. Strikingly, PfMCMBP-deficient parasites complete cytokinesis and form aneuploid merozoites with variable cellular and nuclear sizes. Our study demonstrates that the parasite lacks a robust checkpoint response to prevent cytokinesis following aberrant karyokinesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Cell Nucleus Division*
  • Chromosomes / metabolism
  • Chromosomes / ultrastructure
  • Cytokinesis*
  • Gene Knockdown Techniques
  • Merozoites / cytology
  • Merozoites / growth & development
  • Microtubule-Organizing Center / metabolism
  • Microtubule-Organizing Center / ultrastructure
  • Minichromosome Maintenance Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Plasmodium falciparum / cytology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / metabolism*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Schizonts / physiology


  • Adaptor Proteins, Signal Transducing
  • MCMBP protein, human
  • Nuclear Proteins
  • Protozoan Proteins
  • Minichromosome Maintenance Proteins