De la mimesis al hedonismo y la violencia

Normal cell cycle progression is crucial for proper plant growth and development (De Veylder et al., 2011). The cell cycle chiefly uses the same cellular machinery for meiosis, mitosis and endoreduplication processes (Breuer et al., 2010, Chevalier et al., 2011, De Veylder et al., 2011). The cell cycle is generally divided into four stages; G1 (gap 1), S (DNA synthesis), G2 (gap 2) and M (mitosis) (Breueret al., 2010; Chevalier et al., 2011; De Veylder et al., 2011). Cells grow in number by cell division and expand in size through endoreduplication (De Veylder et al., 2011). In endoreduplication, genome (DNA) of the cell replicates, however, the cell does not divide and re-enters into the cell cycle for the next round of replication, resulting in the duplication of the original genome (Chevalier et al., 2011; De Veylder et al., 2011). Cell cycle progression is integrally regulated and progressed through the activities of a number of cyclin-dependent kinases (CDK) and their respective cyclins. CDK inhibitors (CKIs), such as, KIP-RELATED PROTEINS (KRPs), SIAMESE (SIM) and SIAMESE-RELATED (SMR), also play a central role in the regulation and progression of cell cycle (Kasili et al., 2010). CDK activities are shown to be higher during G1/S and G2/M transitions, however, mitotic CDK activities are repressed during endoreduplication (Inagaki and Umeda, 2011).

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Despite many studies, the switching from the mitotic to the endocycle is poorly understood. Mitotic CDK activity is believed to be reduced or repressed, and this repression of mitotic CDK activity is shown to be achieved through the activation of the anaphase-promoting complex/cyclosome (APC/C). Thus, APC/C is shown to be an important point of convergence for cell division and endoreduplication signalling switching (Peters, 2006, Marrocco et al., 2010, Inagaki and Umeda, 2011). APC, a multi-subunit E3 ubiquitin ligase, essentially controls cell cycle progression through the degradation of cell cycle proteins (Peters, 2006, Marrocco et al., 2010). FIZZY-RELATED (FZR), CELL DIVISION CYCLE 20 (CDC20) and CDH HOMOLOG 1 (CDH1) are shown to be positive activators of APC (Peters, 2006, Larson-Rabin et al., 2009, Marrocco et al., 2010). Five homologues of CDC20 (CDC20.1-CDC20.5) and three homologues of CDH1 (CCS52A1, CCS52A2, and CCS52B) are reported in Arabidopsis. Of three CDH1 homologues, CCS52A1 and CCS52A2 both are implicated in endoreduplication (Lammens et al., 2008, Larson-Rabin et al., 2009, Vanstraelen et al., 2009, Kasili et al., 2010). On the other hand, a number of APC negative regulators such as, OSD1 (OMISSION OF SECOND DIVISION 1), GIG1 (GIGAS cell 1) and UVI4 (UV INSENSITIVE 4) have also been found (Hase et al., 2006, Heyman et al., 2011, Iwata et al., 2011). In conclusion, the proper progression of cell division and endoreplication is of key importance for normal cell growth and development.

As shown, cpr5 plants show smaller leaves, aberrant trichomes and reduced ploidy levels, all of which are dependent on cell cycle for their cell division and expansion through endoreduplication (Bowling et al., 1997, Kirik et al., 2001). These results further highlight that cell cycle (cell division or endoreduplication) appears to be disturbed in cpr5, since epidermal pavement cells of cpr5 were found to be significantly (70 %) smaller than wildtype. A comparison of ploidy levels (DNA content) of cpr5-2 and CPR5 plants revealed that the number of cells having 16C DNA content is greatly (~90 %) reduced in cpr5 compared to wildtype (Kirik et al., 2001). Similarly, trichomes on cpr5 leaves were found to have either none, or contain one appendage and showed reduced ploidy levels (Brininstool et al., 2008). Since cell size and ploidy levels are positively correlated with endoreplication (Brininstool et al., 2008), smaller cells and reduced ploidy levels in cpr5 show that the regulation of cell cycle especially the endocycle, appear to be distorted in cpr5 plants. In contrast to the wildtype, the majority of cpr5 leaf cells and trichomes contain 8C DNA content, while few cells contain 16C ploidy levels (Kirik et al., 2001). These results (the presence of 8C and 16C nuclei) indicate

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that cell cycle or cells are able to enter into the endocycle, however, their entry is somehow restricted past the second round of replication, allowing only a few cpr5 cells to enter in the third round of endoreduplication. How CPR5 exerts an effect on the restriction of the endocycle in cpr5 is not shown yet, and is an interesting question to be answered. A number of studies focus on understanding the role or effect of CPR5 in the regulation of cell cycle, as discussed below.

Endoreduplication is found to be promoted in osd1 and uvi4 loss-of-function mutants when these genes are mutated individually. However, the lethality of female gamete is observed when mutated collectively in osd1uvi4 double mutants (Kasili et al., 2010). Epistatic analyses were carried out between osd1, uvi4 and cpr5 in order to find out the role of CPR5 in endoreduplication. The results show that cpr5 managed to supress the majority of uvi4 ectopic phenotypes (enhanced endocycles) and lethality of osd1uvi4 double mutants. The severity of aberration of trichome appendages and resistance observed in cpr5 was found to be increased in cpr5uvi4(Bao and Hua, 2014). In addition, cell cycle (cyclin B) genes, CYCB1;1, CYCB1;2

and CYCB1;4, were shown to be upregulated in cpr5, which indicates that mitotic activity was higher in cpr5. Based on their results, Bao and Hua, (2014) concluded that CPR5 interacts with OSD1 and UVI4 in a highly complex (unknown) network where CPR5 appears to affect cell cycle signalling downstream of OSD1, UVI4 and FZR (CCS52A) genes.

GL1 ENHANCER BINDING PROTEIN (GeBP) or GeBP-like proteins (GPLs) are putative activators of the GLABRA1 (GL1) gene, which is required for normal cuticle and trichome formation as well as plant defence responses (Xia et al., 2010). GeBL/GPLs overlap with CPR5 signalling and are found to activate a set of genes, which represents a subset of CPR5 signalling pathway genes induced in cpr5(Perazza et al., 2011). This CPR5 subset of genes is shown to be implicated in cell expansion and endoreplication in a CPR5 dose-dependent manner (Perazza et al., 2011). Despite the aforementioned studies, little is known about the direct role of CPR5 in the cell cycle, and specifically in endoreduplication regulation.

In 2014, the CPR5 was shown to physically interact with CKIs, such as, KRP2, SIM and SMR (Wang et al., 2014b). Additionally, it was proposed that CKIs are safeguarded by CPR5 in the nuclear membrane, which are released upon pathogen detection by NB-LLR and subsequently phosphorylate RB-E2F signalling in order to initiate cell cycle progression (Wang et al., 2014b). Recently, CPR5 has emerged as one of the nucleoporins of the nuclear pore complex

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(NPC) and has been shown to restrict the entry of an array of nuclear cargoes (Gu et al., 2016). Gu and co-workers also proposed that CKIs are dissociated from CPR5, phosphorylate RB- E2F signalling and induce cell cycle progression upon pathogen recognition (Gu et al., 2016). In cpr5, the proper shutting and opening of the NPC is compromised, which in turn results in the deregulated entry of a large number of molecules in the nucleus that could lead to intrusions in a number of pathways (Gu et al., 2016). Aberrant phenotypes and disruptions in various pathways could be a consequence of loss of gating ability of CPR5. To summarize, these results show that cell cycle and endoreduplication is affected in cpr5, the exact mechanism of which is not understood yet.