ABSTRACT

At the Start transition in G1, budding yeast cells integrate internal and external cues into an all-or-none commitment to a new round of cell division [1],[2]. Cell division is asymmetric, producing a smaller daughter cell and a larger mother cell [3]. Mother cells progress through Start more quickly than daughter cells [3],[4]. The regulation of G1 phase is composed of two independent modules separated by the nuclear exit of the transcriptional repressor Whi5 [5]: a cell size sensing module, which extends G1 in small cells to allow additional growth before Start [5], and a subsequent sizeindependent module [5],[6]. The fast and coherent transition between the two modules likely coincides with commitment to the cell cycle and is driven by transcriptional positive feedback [7]. The G1 cyclin Cln3 is the

most upstream activator of the Start transition [8],[9],[10],[11],[12] and the main regulator of the size-sensing module. Cln3 initiates inactivation of Whi5 [13],[14] and expression of SBF/MBF dependent genes, including the G1 cyclins CLN1 and CLN2 [9],[11],[12],[15],[16]. Subsequent positive feedback of Cln1 and Cln2 on SBF/MBF dependent transcription ensures fast and coherent commitment to the cell cycle [7].