Tsekrekou Maria, Stratigi Kalliopi, Chatzinikolaou Georgia
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
Department of Biology, University of Crete, Vassilika Vouton, 71409 Heraklion, Crete, Greece.
Int J Mol Sci. 2017 Jul 1;18(7):1411. doi: 10.3390/ijms18071411.
The nucleolus is the subnuclear membrane-less organelle where rRNA is transcribed and processed and ribosomal assembly occurs. During the last 20 years, however, the nucleolus has emerged as a multifunctional organelle, regulating processes that go well beyond its traditional role. Moreover, the unique organization of rDNA in tandem arrays and its unusually high transcription rates make it prone to unscheduled DNA recombination events and frequent RNA:DNA hybrids leading to DNA double strand breaks (DSBs). If not properly repaired, rDNA damage may contribute to premature disease onset and aging. Deregulation of ribosomal synthesis at any level from transcription and processing to ribosomal subunit assembly elicits a stress response and is also associated with disease onset. Here, we discuss how genome integrity is maintained within nucleoli and how such structures are functionally linked to nuclear DNA damage response and repair giving an emphasis on the newly emerging roles of the nucleolus in mammalian physiology and disease.
核仁是一种无膜的亚核细胞器，rRNA在此进行转录、加工以及核糖体组装。然而，在过去20年里，核仁已成为一种多功能细胞器，其调控的过程远远超出了其传统作用。此外，rDNA以串联阵列形式存在的独特组织方式及其异常高的转录速率，使其容易发生非程序性DNA重组事件以及频繁形成RNA:DNA杂交体，进而导致DNA双链断裂（DSB）。如果不能得到妥善修复，rDNA损伤可能会导致疾病过早发生和衰老。从转录、加工到核糖体亚基组装的任何水平上核糖体合成的失调都会引发应激反应，并且也与疾病的发生有关。在此，我们讨论核仁内基因组完整性是如何维持的，以及这些结构如何在功能上与核DNA损伤反应和修复相联系，重点阐述核仁在哺乳动物生理学和疾病中的新出现的作用。
