SET Domain Protein Regulates S. pombe Cytokinesis Figure 8. Identification of S. pombe genes differentially expressed with respect to genotype. Volcano plot (left panels) and scatter plot (right panels) analysis of the expression of all S. pombe genes in DMSO (A) or LatA (B) treated cells of the indicated genotype. Horizontal green lines in volcano plots represent a p-value of 0.05. Vertical green lines in volcano plots represent threshold for a 1.5 fold change in expression. Red squares in volcano plots indicate differentially expressed genes. Diagonal green lines in scatter plots represent the threshold for a 1.5 fold change in expression. The color of the squares in scatter plots indicates the level of expression of that gene in DMSO (A) or LatA (B) treated wild-type cells. doi:10.1371/journal.pone.0031224.g008 The importance of understanding the pathways required for the dependable execution of cytokinesis in eukaryotes was first articulated by Theodor Boveri almost 100 years ago [26]. In his classic work ‘‘Concerning the origin of malignant tumours’’ (1914) Boveri hypothesized that tetraploid intermediates – derived from either cytokinetic failure or cell fusion – might undergo chaotic multipolar mitoses leading to numerical and/or structural chromosomal defects. Recent experimental evidence provides strong support for Boveri’s assertions. First, tetraploid mouse mammary epithelial cells generated by the inhibition of cytokinesis display increased rates of aneuploidy and (when transplanted into nude mice) give rise to malignant tumours at greater rates than controls [27]. Second, tetraploidy often precedes gross aneuploidy and is an early event in carcinogenesis [28,29]. Third, aneuploidy (generated by loss of the kinesin, Kif4) promotes tumorigenesis in vivo [30]. Lastly, several tumor suppressors (BRCA2, LATS) are required for the completion of cytokinesis [31,32]. Taken together these results suggest that mechanisms promoting the dependable execution of cytokinesis are important in maintaining genomic integrity and in preventing carcinogenesis [33,34,35]. Thus, in the broadest sense, an understanding of these pathways may provide a better understanding of one ‘‘route’’ by which eukaryotic cells become tumorigenic in multicellular organisms. Given the importance of cytokinesis in maintaining genomic integrity it is particularly intriguing to note that orthologues of Hif2p, Set3p, and Snt1p exist in humans (TBL1X, MLL5, and NCOR2, respectively). Furthermore – as might be expected based on the selection criteria used in the genetic screen – MLL5, PLoS ONE | www.plosone.org 10 February 2012 | Volume 7 | Issue 2 | e31224