Questioning the G2 phase in the budding yeast cell cycle with a qualitative and possibilistic model

Abstract

The budding yeast S. cerevisiae, a foundational model for cell cycle studies, exhibits a complex phase organisation (G1, S, G2/M) governed by checkpoints ensuring faithful cellular inheritance. However, the existence of a distinct G2 phase in yeast remains debated, with some advocating for a prometaphase instead. To address this issue, we developed a discrete-event, qualitative, and possibilistic model, the first one to our knowledge, to integrate organelle-level components (replication forks, sister chromatids, mitotic spindle, bud) while remaining parsimonious. Unlike molecular-centred or overly complex whole-cell models, this approach bridges broad systemic and finer mechanistic scales. Our results demonstrate that the model faithfully recapitulates cell cycle progression and supports the dispensable G2 phase. This possibilistic model inspired from recent applications in ecology advocates in favor of the necessity of prometaphase. This study thus provides a unifying and flexible framework to resolve long-standing ambiguities in yeast cell dynamics, while avoiding the pitfalls of excessive complexity or reductionism.