The nucleus as a regulator of the cell cycle. How mechanical perturbations affect the length of the G1 phase.

Regarded as the seed of any form of life, the cell is a complex and stunning system capable of performing a great variety of tasks. In order to properly complete its functionalities, precise mechanisms of control are necessary during the cell life (i.e. the cell cycle). Among them, great importance is given to the ones related to size homeostasis; indeed, experimental evidence has shown that size is cell type-specific and is important in monitoring cell function. The actual state of knowledge in the field has identified three main 'checkpoints' for this regulation: the reduction or starting point, at the G1/S transition, which defines the border between growth and DNA replication; a checkpoint at the G2/M transition, which is related to the division between the pre-mitotic phase and the mitotic one; and the spindle checkpoint that ensures the correct progress of the mitotic phase. The former has attracted great interest already in the past since the length of the G1 phase seems to be the most variable during the cell cycle. Experimental observations have demonstrated that the compression of the nucleus is fundamental to undergo the G1/S transition and that this flattening is strictly connected to a delicate balance of fluxes of metabolites inward and outward of the nucleoplasm. This work will present the theoretical grounds of the hypothesis suggested by the team of Matthieu Piel at the Institute Curie (Paris): the nuclear tension is proposed as a key parameter that couples cell size homeostasis and cell cycle length regulation. The analyses of this tension and how it affects the nuclear shape, the hypothesis of a critical value for the tension that triggers the G1/S transition and its connection with the variability of duration of the G1 phase are the main subjects of this study which allow to go deeper into the understanding of the cell cycle and of the diseases related to its misfunction.