Xeroderma pigmentosum (XP) is an ultraviolet light-sensitivity syndrome caused by nucleotide excision repair (NER) defects, resulting in hyperpigmentation and an increased incidence of skin cancer. These symptoms also characterize the skin ‘telopathies’, which result from accelerated telomere shortening and exhaustion of the regenerative capacity of stem cells and lead to premature death. In this issue, Gerdine Stout and Maria Blasco investigate the pathways that connect stem cell dysfunction with telomere uncapping using a mouse model of telomere dysfunction which phenocopies the symptoms of XP patients. They demonstrate that both the absence of NER and the abrogation of p53 activity restore stem cell functionality. This work highlights the relationship between telomeres and stem cell renewal with the pathobiology of cancer.

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2009