Adult stem cells fuel tissue homeostasis and regeneration through their unique ability to self-renew and differentiate into specialized cells. Thus, their DNA provides instructions that impact the tissue as a whole. Since DNA is not an inert molecule, but rather dynamic, interacting with a myriad of chemical and physical factors, it encounters damage from both endogenous and exogenous sources. Damage to DNA introduces deviations from its normal intact structure and, if left unrepaired, may result in a genetic mutation. In turn, mutant genomes of stem and progenitor cells are inherited in cells of the lineage, thus eroding the genetic information that maintains homeostasis of the somatic cell population. Errors arising in stem and progenitor cells will have a substantially larger impact on the tissue in which they reside than errors occurring in postmitotic differentiated cells. Therefore, maintaining the integrity of genomic DNA within our stem cells is essential to protect the instructions necessary for rebuilding healthy tissues during homeostatic renewal. In this review, we will first discuss DNA damage arising in stem cells and cell- and tissue-intrinsic mechanisms that protect against harmful effects of this damage. Secondly, we will examine how erroneous DNA repair and persistent DNA damage in stem and progenitor cells impact stem cells and tissues in the context of cancer initiation and aging. Finally, we will discuss the use of invertebrate and vertebrate model systems to address unanswered questions on the role that DNA damage and mutation may play in aging and precancerous conditions.

中文翻译：

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衰老和癌症发病背景下的干细胞 DNA 损伤和基因组突变。

成体干细胞通过其独特的自我更新和分化成特化细胞的能力促进组织稳态和再生。因此，他们的 DNA 提供了影响整个组织的指令。由于 DNA 不是惰性分子，而是动态的，与无数的化学和物理因素相互作用，它会遇到内源性和外源性来源的损害。DNA 受损会导致其正常的完整结构出现偏差，如果不加以修复，可能会导致基因突变。反过来，干细胞和祖细胞的突变基因组在谱系的细胞中遗传，从而侵蚀维持体细胞群稳态的遗传信息。与有丝分裂后分化细胞中发生的错误相比，干细胞和祖细胞中出现的错误对它们所在的组织的影响要大得多。因此，保持我们干细胞内基因组 DNA 的完整性对于保护在稳态更新期间重建健康组织所必需的指令至关重要。在这篇综述中，我们将首先讨论干细胞中产生的 DNA 损伤以及防止这种损伤的有害影响的细胞和组织内在机制。其次，我们将研究干细胞和祖细胞中错误的 DNA 修复和持续的 DNA 损伤如何在癌症发生和衰老的背景下影响干细胞和组织。最后，