Identification of new cell size control genes in S. cerevisiae

Cell size homeostasis is physiologically important to nearly all organisms. This is evident from the uniformity and conservation of size within a cell lineage amongst the individuals of a species from bacteria to man [1]. Moreover, studies in flies, mice and humans indicate the presence of an organ size checkpoint during developmental stages [2]. To ensure a population of cells that maintain a constant average cell size, it is essential that cells coordinate the processes of growth, which increases cell size, and cell division, which reduces cell size [3]. Irregularities in these processes affect fitness and function [4]. In the budding yeast S. cerevisiae, coordination of growth and division occurs at START, the point of commitment to the cell cycle [5,6] which is equivalent to the Restriction point in mammalian cells [7]. At START, a cell transits, essentially irreversibly, from G1- to S-phase. Early genetic analyses of START revealed that blocking cell growth prevents cell cycle progression [5]. However, the converse is not true [5]. For example, the discovery of cell division cycle (CDC) genes, a class of essential genes involved in cell cycle control, established that cell growth is a continuous process that proceeds unabated even when cell cycle progression is halted [8]. The end result is the production of abnormally large cells [5]. Thus, the mechanisms that regulate the cell cycle can have a profound impact on cell growth and vice versa.Physiological studies in yeast and mammalian cells suggest that cells undergo exponential growth throughout the cell cycle [4,9-12]. Since exponential growth is inherently tied to cell size (e.g. larger cells grow faster than smaller cells), some type of “size sensing” mechanism is required for cell size homeostasis [4,13,14]. While the mechanism remains somewhat obscure, evidence suggests that in yeast commitment to division is linked to cell size [4,13,14]. In yeast, cells must attain a certain “critical cell size” before