G-Quadruplex Assembly by Ribosomal DNA: Emerging Roles in Disease Pathogenesis and Cancer Biology.
G-Quadruplex Assembly by Ribosomal DNA: Emerging Roles in Disease Pathogenesis and Cancer Biology.
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DOI：
10.1159/000516394
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发表时间：
2021
影响因子：
1.7
通讯作者：
Brosh RM Jr
中科院分区：
文献类型：
--
作者：
Datta A;Pollock KJ;Kormuth KA;Brosh RM Jr
真核基因组的独特重复元件可能会给细胞 DNA 复制和转录带来问题，并成为基因组不稳定的根源。人类核糖体 DNA (rDNA) 以聚集在多条染色体上的重复单位的形式存在。了解 rDNA 干扰正常基因组稳态的分子机制是本综述的主题。我们讨论了 rDNA 作为衰老驱动因素的不稳定性以及解旋酶在抑制其有害影响方面的重要作用。富含鸟嘌呤碱基的核糖体 DNA 形成 G-四链体 (G4) 的倾向在疾病发病机制中进行了讨论和评估。以核糖体和其他染色体位点中的 G4 为靶点可能代表了一种对抗癌症的有用的合成致死方法。
Unique repetitive elements of the eukaryotic genome can be problematic for cellular DNA replication and transcription and pose a source of genomic instability. Human ribosomal DNA (rDNA) exists as repeating units clustered together on several chromosomes. Understanding the molecular mechanisms whereby rDNA interferes with normal genome homeostasis is the subject of this review. We discuss the instability of rDNA as a driver of senescence and the important roles of helicases to suppress its deleterious effects. The propensity of ribosomal DNA that is rich in guanine bases to form G-quadruplexes (G4) is discussed and evaluated in disease pathogenesis. Targeting G4 in the ribosomes and other chromosomal loci may represent a useful synthetic lethal approach to combating cancer.