In DC and the related inherited bone-marrow failure syndrome Fanconi anaemia, loss of the hematopoietic stem cell niche is accompanied by activation of the p53/p21 axis, inducing a replicative senescent phenotype.45, 46, 47 Furthermore, studies on transgenic mouse models of nucleotide deficiency reported that the fine-tuning of nucleotide metabolism pathways is required for resolution of replication stress and overcoming maturation defects of hematopoietic stem and progenitor cells in vivo.48 Here, TP53 is linked to Fanconi anemia.