Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis.
Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis.
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DOI：
10.1038/s41388-017-0121-z
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发表时间：
2018-05
期刊：
影响因子：
8
通讯作者：
Volarevic S
中科院分区：
文献类型：
--
作者：
Lindström MS;Jurada D;Bursac S;Orsolic I;Bartek J;Volarevic S
核仁是合成核糖体的主要场所，核糖体是负责蛋白质合成的复杂分子机器。过去20年的大量研究已经清楚地表明，核糖体生物发生的定量和定性改变都可以通过蛋白质合成的失调来驱动恶性表型。然而，许多最近的蛋白质组学，基因组学和功能的研究表明，核仁的调节过程是无关的核糖体生物合成，包括DNA损伤反应，基因组稳定性和空间组织的维护，表观遗传调控，细胞周期控制，应激反应，衰老，全球基因表达，以及组装或成熟的各种核糖核蛋白颗粒。在这篇综述中，重点将是rDNA基因的功能，这使得他们非常容易受到DNA损伤和染色体内和染色体间重组以及内置的机制，防止和修复rDNA损伤，以及如何失调，这种相互作用影响全基因组DNA的稳定性，基因表达和常染色质和异染色质之间的平衡。我们还将介绍这些细胞过程的功能障碍如何成为人类恶性肿瘤的核心驱动力的最新见解，并提出一种有前途的治疗癌症的新方法。
The nucleolus is the major site for synthesis of ribosomes, complex molecular machines that are responsible for protein synthesis. A wealth of research over the past 20 years has clearly indicated that both quantitative and qualitative alterations in ribosome biogenesis can drive the malignant phenotype via dysregulation of protein synthesis. However, numerous recent proteomic, genomic, and functional studies have implicated the nucleolus in the regulation of processes that are unrelated to ribosome biogenesis, including DNA-damage response, maintenance of genome stability and its spatial organization, epigenetic regulation, cell-cycle control, stress responses, senescence, global gene expression, as well as assembly or maturation of various ribonucleoprotein particles. In this review, the focus will be on features of rDNA genes, which make them highly vulnerable to DNA damage and intra- and interchromosomal recombination as well as built-in mechanisms that prevent and repair rDNA damage, and how dysregulation of this interplay affects genome-wide DNA stability, gene expression and the balance between euchromatin and heterochromatin. We will also present the most recent insights into how malfunction of these cellular processes may be a central driving force of human malignancies, and propose a promising new therapeutic approach for the treatment of cancer.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
64.8
作者：
Burrell RA;McClelland SE;Endesfelder D;Groth P;Weller MC;Shaikh N;Domingo E;Kanu N;Dewhurst SM;Gronroos E;Chew SK;Rowan AJ;Schenk A;Sheffer M;Howell M;Kschischo M;Behrens A;Helleday T;Bartek J;Tomlinson IP;Swanton C
通讯作者：
Swanton C
影响因子：
64.5
作者：
Bassermann, Florian;Frescas, David;Guardavaccaro, Daniele;Busino, Luca;Peschiaroli, Angelo;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
5.3
作者：
Akamatsu, Yufuko;Kobayashi, Takehiko
通讯作者：
Kobayashi, Takehiko
影响因子：
5.3
作者：
Colombo, E;Bonetti, P;Pelicci, PG
通讯作者：
Pelicci, PG