The telomere checkpoint.

Loss of telomere repeats following replication and oxidative damage results in activation of a DNA damage signal that triggers DNA repair reactions involving telomerase and/or molecules involved in recombination such as BRCA1, WRN, and BLM. Following effective repair, cells can go through another round of cell division. However, eventually too many short telomeres accumulate for the limited telomere repair capacity. The resulting high levels of p53 will trigger apoptosis or replicative senescence. Because telomerase levels are limiting in hematopoietic stem cells, such a threshold will be reached earlier in cells that express subnormal levels of telomerase, as in dyskeratosis congenita.