Plasmodium Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Rajan Pandey,Steven Abel,Matthew Boucher,Richard J Wall,Mohammad Zeeshan,Edward Rea,Aline Freville,Xueqing Maggie Lu,Declan Brady,Emilie Daniel,Rebecca R Stanway,Sally Wheatley,Gayani Batugedara,Thomas Hollin,Andrew R Bottrill,Dinesh Gupta,Anthony A Holder,Karine G Le Roch,Rita Tewari

doi:10.1016/j.celrep.2020.01.033

Abstract

SummaryCondensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle.

Highlights

Cellular proliferation in eukaryotes requires chromosome replication and segregation, followed by cell division, to ensure that daughter cells have identical copies of the genome
We found the P. berghei SMC4 N-terminal ATPase domain divided in two by a 44 amino acid insertion; a similar pattern has been observed in other Plasmodium species
We generated a 3D model of the P. berghei SMC2 and SMC4 ATPase head domains and partial coiled region using homology-based 3D structure modeling (Figure 1D)

Summary

Introduction

Cellular proliferation in eukaryotes requires chromosome replication and segregation, followed by cell division, to ensure that daughter cells have identical copies of the genome. During classical open mitosis in many eukaryotes, chromosome condensation, centrosome migration, and formation of the mitotic spindle are followed by dissolution of the nuclear envelope (Gu€ttinger et al, 2009). An essential component of chromosome dynamics is a family of structural maintenance of chromosomes proteins, originally described in budding yeast as stability of minichromosomes (SMC) proteins, which are implicated in chromosome segregation and condensation (Hirano, 2016; Uhlmann, 2016). The six SMCs can be classified as subunits of condensin (SMC2 and SMC4, required for chromosomal condensation), cohesin (SMC1 and SMC3, required for chromosomal segregation), and the SMC5-SMC6 complex (involved in DNA repair and homologous recombination) (Hirano, 2016; Uhlmann, 2016)

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Discussion

Conclusion