The various molecular elements that control cell cycle progression allowing cell division are organized hierarchically, giving rise to a series of precisely regulated events in space and time. In all eukaryotes studied to date, cell division is controlled by an evolutionarily conserved molecular machinery wherein specific genes fundamental to animal cell cycle control have orthologs in other eukaryotes like plants and vice versa. Nevertheless, neither all the genetic elements associated to this machinery are known nor their interaction dynamics understood.Here we implemented literature mining, coexpression analyses and comparative genomics tools to further explore the gene list of 339 candidates proposed by Quimbaya and colleagues, filtering out new cell cycle regulators in Arabidopsis thaliana that, additionally, derived from orthology inference, had a high potential of being involved in carcinogenic events in humans, given their functional relation with already known cancer genes.Some of the new cell cycle regulators detected by our strategy were phenotypically analyzed using A. thaliana mutants. This experimental characterization showed that the reduced expression of the AtPME1 gene is directly associated with mutant plants with altered epidermal phenotypes, an archetypical mark of cell cycle alteration, validating experimentally our designed strategy. Additionally, from our findings, we hypothesize that AtPME1 plays a role during endocycle entry.These newly studied genetic elements in Arabidopsis thaliana will deepen our understanding about cell cycle regulation in plants, whereas its human orthologs could represent excellent candidates for future experimental characterization as a potential oncogenes or tumor suppressor during carcinogenic transformation.