The study investigates the role of p53 in preventing the reprogramming of cells with various types of DNA damage, including short telomeres, DNA repair deficiencies, or exogenously inflicted DNA damage, into induced pluripotent stem (iPS) cells. The authors found that p53 is crucial in limiting the reprogramming efficiency by inducing apoptosis of suboptimal cells at the time of pluripotency induction. In the presence of pre-existing DNA damage, p53-dependent apoptosis is activated, leading to the elimination of damaged cells and preventing them from becoming iPS cells. The study also shows that p53-deficient cells exhibit increased chromosomal instability, with higher frequencies of end-to-end fusions and chromosomal breaks/fragments. These findings suggest that p53 plays a critical role in ensuring the genomic integrity of iPS cells by limiting the reprogramming of cells with suboptimal DNA damage.The study investigates the role of p53 in preventing the reprogramming of cells with various types of DNA damage, including short telomeres, DNA repair deficiencies, or exogenously inflicted DNA damage, into induced pluripotent stem (iPS) cells. The authors found that p53 is crucial in limiting the reprogramming efficiency by inducing apoptosis of suboptimal cells at the time of pluripotency induction. In the presence of pre-existing DNA damage, p53-dependent apoptosis is activated, leading to the elimination of damaged cells and preventing them from becoming iPS cells. The study also shows that p53-deficient cells exhibit increased chromosomal instability, with higher frequencies of end-to-end fusions and chromosomal breaks/fragments. These findings suggest that p53 plays a critical role in ensuring the genomic integrity of iPS cells by limiting the reprogramming of cells with suboptimal DNA damage.