Toward identifying a cellular determinant of telomerase repression.

Normal human cells undergo an irreversible growth arrest after a limited number of cell divisions (1,2). In contrast, a hallmark of most cancer cells is their ability to divide an unlimited number of times. Lately, the importance of counteracting the limitations of normal cell growth as a cellular requirement for cancer progression has become appreciated (3–5). There is evidence for a genetic basis of cellular aging. Thus, somatic cell hybrids between immortal cancer cells and normal cells are mortal, demonstrating that cellular aging/senescence is dominant over immortality (6). These findings have been pursued in an attempt to identify specific genes regulating these processes. Microcell-mediated chromosome transfer has provided mounting evidence that there are several senescence-specific genetic pathways (7). In some instances, the introduction of specific chromosomes or genes into proliferating cells results in a rapid growth arrest, suggesting that a senescence-like stress response may quickly induce cell cycle checkpoints. In other instances, there is a significant delay after chromosome transfer until the growth arrest. Recent progress in understanding the basis for this latter observation is the subject of this editorial.