Department of Biology, University of Rome "Tor Vergata," 00173 Rome, Italy; Regina Elena National Cancer Institute, 00144 Rome, Italy.
Department of Biology, University of Rome "Tor Vergata," 00173 Rome, Italy.
Mol Cell. 2017 May 4;66(3):306-319. doi: 10.1016/j.molcel.2017.04.006.
Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions. Such a resistance contributes to the genetic drift of evolving tumors as well as to their limited sensitivity to chemo- and radiotherapy. Here, we discuss the pathophysiological and therapeutic implications of the molecular pathways through which stem cells cope with DNA damage.
胚胎和成体干细胞都具有优越的能力，可以防止遗传损伤的积累、修复它们，或避免其在子细胞中传播，这对整个生物体尤其不利。诱导多能干细胞也表现出强大的 DNA 损伤反应，但它们基因组的稳定性通常受到起源细胞群体的突变历史的影响，这构成了临床应用的障碍。癌症干细胞对 DNA 损伤特别耐受，并且在遗传损伤积累时不会经历衰老或受调控的细胞死亡。在这里，我们讨论了干细胞应对 DNA 损伤的分子途径的病理生理和治疗意义。
