Genome Re-duplication and Irregular Segregation Occur During the Cell Cycle of Entamoeba histolytica

Abstract

Heterogeneity of genome content is commonly observed in axenic cultures of Entamoeba histolytica. Cells with multiple nuclei and nuclei with heterogenous genome contents suggest that regulatory mechanisms that ensure alternation of DNA synthesis and mitosis are absent in this organism. Therefore, several endo-reduplicative cycles may occur without mitosis. The data also shows that unlike other endo-reduplicating organisms, E.histolytica does not undergo a precise number of endo-reduplicative cycles. We propose that irregular endo-reduplication and genome partitioning lead to heterogeneity in the genome content of E.histolytica trophozoites in their proliferative phase. The goal of future studies should be aimed at understanding the mechanisms that are involved in (a) accumulation of multiple genome contents in a single nucleus; (b) genome segregation in nuclei that contain multiple genome contents and (c) maintenance of genome fidelity in E. histolytica.

Entamoeba histolytica EhDEAD1 is a conserved DEAD-box RNA helicase with ATPase and ATP-dependent RNA unwinding activities

“…It has been suggested that surveillance mechanisms or checkpoints regulating alternation of genome duplication and cell division are altered or absent in E. histolytica. Sequence homologous to several cell cycle regulating proteins have been identified in amoeba, but their structural divergence suggests that they may not have equivalent function in this organism (Banerjee et al, 2002;Lohia, 2003;Loftus et al, 2005;Lohia et al, 2007). Constitutive association of the evolutionary conserved EhMcm2-3-5 proteins with chromatin could be one of the reasons why genome reduplication occurs in E. histolytica (Das et al, 2005).…”

Entamoeba histolytica Encodes Unique Formins, a Subset of Which Regulates DNA Content and Cell Division

“…Log-phase cultures may accumulate multinucleated cells containing heterogeneous amounts of DNA (12,18). Our previous observations suggest that genome reduplication without mitosis and irregularity in cytokinesis contribute maximally to the observed heterogeneity (12,36). We have also observed that sequence homologs of several eukaryotic "checkpoint proteins" are not found in the amoeba genome (36).…”

“…Our previous observations suggest that genome reduplication without mitosis and irregularity in cytokinesis contribute maximally to the observed heterogeneity (12,36). We have also observed that sequence homologs of several eukaryotic "checkpoint proteins" are not found in the amoeba genome (36). However, functional analysis of a kinesin-like protein, E. histolytica Klp5 (Klp5 Eh ), showed that increased expression of this protein, while promoting microtubular spindles, leads to homogenization of the average DNA content in growing cells (13).…”

“…The cell division cycle of E. histolytica trophozoites in axenic culture shows very unusual features (36). Log-phase cultures may accumulate multinucleated cells containing heterogeneous amounts of DNA (12,18).…”

Structure of Ca2+-binding protein-6 from Entamoeba histolytica and its involvement in trophozoite proliferation regulation

“…histolytica has been shown to occur along the microtubular assemblies without disruption of the nuclear envelope [20,21]. Occurrence of multinucleated cells in cell culture suggested duplication and reduplication of nuclear DNA without cytokinesis [22,23]. Although Kinesin like protein (Klp1), Formin1 and EhCaBP6 were shown to be part of the microtubular assembly [19,24,25], their role in regulation of the cell cycle is not yet documented.…”