More than half of the human genome consists of repetitive sequences, with the ribosomal DNA (rDNA) representing two of the largest repeats. Repetitive rDNA sequences may form a threat to genomic integrity and cellular homeostasis due to the challenging aspects of their transcription, replication, and repair. Predisposition to cancer, premature aging, and neurological impairment in ataxia-telangiectasia and Bloom syndrome, for instance, coincide with increased cellular rDNA repeat instability. However, the mechanisms by which rDNA instability contributes to these hereditary syndromes and tumorigenesis remain unknown. Here, we review how cells govern rDNA stability and how rDNA break repair influences expansion and contraction of repeat length, a process likely associated with human disease. Recent advancements in CRISPR-based genome engineering may help to explain how cells keep their rDNA intact in the near future.

中文翻译：

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保持核糖体DNA完整：一个重复的挑战。

人类基因组的一半以上由重复序列组成，其中核糖体DNA（rDNA）代表两个最大的重复序列。重复的rDNA序列由于其转录，复制和修复的挑战性方面，可能对基因组完整性和细胞体内平衡构成威胁。例如，共济失调毛细血管扩张症和布卢姆综合症易患癌症，过早衰老和神经系统受损，这与细胞rDNA重复序列不稳定性增加有关。但是，rDNA不稳定性促成这些遗传综合征和肿瘤发生的机制仍然未知。在这里，我们回顾了细胞如何控制rDNA的稳定性以及rDNA的断裂修复如何影响重复长度的扩增和收缩，这可能与人类疾病有关。