The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells. In this review, we discuss what is known about the differences between stem cells and somatic cells regarding chromosome end protection.
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