Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction

p53 activates Puma-dependent apoptosis and p21-mediated cell-cycle arrest in response to DNA damage. Rudolph and colleagues show that stem-cell functionality in telomerase-deficient mice is improved by the deletion of Puma. Unexpectedly, the accumulation of progenitor cells with damaged short-telomere DNA is not seen in telomerase- and Puma-deficient animals, as p21-mediated cell-cycle arrest is activated to limit the expansion of these cells.