Approximately 90% of all human cancers, in which some deregulation of cell cycle arrest or programmed cell death has occurred, express telomerase, a ribonucleoprotein whose activity is normally turned off in healthy somatic tissues. Additionally, small populations of self-renewing stem cells, such as hematopoietic stem cells, skin and hair follicle basal layer cells and intestinal basal crypt cells, have been shown to retain telomerase activity. Conversely, hereditary defects that result in shortened telomeres in humans have been shown to manifest most often as bone marrow failure or pulmonary fibrosis, along with a myriad of other symptoms, likely due to the loss of the stem and/or progenitor cells of affected tissues. The aim of this review is to highlight our knowledge of the mechanisms of telomere maintenance that contribute to the pathology of human disease caused by dysfunctional telomere homeostasis. Specifically, a new role for the SNM1B/Apollo nuclease in the pathologies of Hoyeraal-Hreidarsson syndrome will be discussed.

中文翻译：

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人骨髓衰竭综合征中的端粒功能障碍

大约 90% 的人类癌症（其中发生了细胞周期停滞或程序性细胞死亡的一些失调）表达端粒酶，这是一种核糖核蛋白，其活性通常在健康体细胞组织中关闭。此外，少量的自我更新干细胞，如造血干细胞、皮肤和毛囊基底层细胞以及肠基底隐窝细胞，已被证明保留了端粒酶活性。相反，导致人类端粒缩短的遗传性缺陷最常表现为骨髓衰竭或肺纤维化，以及无数其他症状，可能是由于受影响组织的干细胞和/或祖细胞的丧失. 本综述的目的是强调我们对端粒维持机制的了解，这些机制有助于端粒稳态失调引起的人类疾病的病理学。具体而言，将讨论 SNM1B/Apollo 核酸酶在 Hoyeraal-Hreidarsson 综合征病理学中的新作用。