The G 1 interval in the mammalian cell cycle: dual control by mass accumulation and stage‐specific activities

. The temporal determinants of the G 1 cell cycle interval were investigated using nine mammalian cell lines. In each case, cells were allowed to proliferate for many cell cycles under conditions that slowed progress through S phase without an equivalent impairment of overall mass accumulation. This disproportionate inhibition of progress through the cell cycle caused newly produced cells to be more massive than usual. Under these growth conditions, the determinants of the length of the G 1 interval became evident. For two cell lines, HeLa S3 and NIH 3T3, a protracted S phase, and the resultant increase in mass, resulted in a dramatically shortened G 1 interval. Thus, for these cell lines, a major portion of G 1 time exists to accommodate mass accumulation needed to initiate the subsequent S phase. Nevertheless, under conditions that protracted S phase and shortened the G 1 interval, cells still exhibited a measurable G 1 time, reflecting the stage‐specific activities within G 1 . One activity that may be responsible for this obligatory G 1 time is the synthesis of a labile protein. For other cells studied here, protraction of S phase also caused proliferating cells to become more massive, but in these cases there was no diminution of the G 1 time. For these cells, the entire G 1 interval must accommodate G 1‐ specific activities necessary to initiate a new cell cycle. A unifying view of the G 1 interval recognizes the two distinct influences that determine the time spent in G 1 : the need to accumulate sufficient mass to initiate a new DNA‐division sequence; and the stage‐specific events necessary for the subsequent S phase. The length of the G 1 interval is dictated by the longer of these two time‐consuming activities.