Small but mighty: the causes and consequences of micronucleus rupture.
Small but mighty: the causes and consequences of micronucleus rupture.
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DOI：
10.1038/s12276-020-00529-z
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发表时间：
2020-11
影响因子：
12.8
通讯作者：
Lee JH
中科院分区：
文献类型：
--
作者：
Kwon M;Leibowitz ML;Lee JH
细胞核是与主核空间隔离的含有DNA的小核结构。它们经常出现在病理学中，包括癌症。最近的研究表明，这些核结构不仅是疾病的生物标志物，而且在肿瘤生物学中起着积极的作用。微核形成对肿瘤生物学的许多后果取决于其核膜的频繁且不可逆的破裂，这导致其DNA内容物暴露于细胞质。在这篇综述中，我们讨论了有缺陷的核膜沉积在错误分离的染色体上，导致核膜破裂的模型。此外，我们阐述了微核核膜破裂对细胞的各种下游后果。这些后果包括称为chromothripsis的大规模DNA重排现象和cGAS-STING先天免疫信号通路的激活，这可能是一把双刃剑，具有肿瘤发生和肿瘤预防功能。虽然微核是小结构，但它们对细胞及其微环境的影响相当大。包含有缺陷的染色体或染色体片段并发生在主细胞核外的细胞核容易破裂，从而导致DNA变化，从而导致肿瘤的发展。由韩国首尔梨花女子大学的Mijung Kwon和水原Ajou大学医学院的Jae-Ho Lee领导的一个研究小组回顾了这些微核如何倾向于破裂，将其内容物溢出到细胞中，造成毁灭性的后果。它们所包含的染色体断裂成微小的片段，这些断裂的DNA进入主细胞核，导致染色体重排，从而永久改变基因组功能。微核的破裂也激活了先天免疫系统的一部分，可以促进癌细胞的入侵和扩散。针对这些过程的药物可以帮助治疗癌症。
Micronuclei are small DNA-containing nuclear structures that are spatially isolated from the main nucleus. They are frequently found in pathologies, including cancer. It was recently shown that these nuclear structures are not only biomarkers of disease but also play an active role in tumor biology. Many consequences of micronucleus formation on tumor biology are dependent on the frequent and irreversible rupture of their nuclear envelopes, which results in the exposure of their DNA contents to the cytoplasm. In this review, we discuss models of defective nuclear envelope deposition on missegregated chromosomes that lead to nuclear envelope rupture. Furthermore, we expound upon the various downstream consequences of micronucleus nuclear envelope rupture on cells. These consequences include a massive DNA rearrangement phenomenon called chromothripsis and activation of the cGAS-STING innate immune signaling pathway, which can be a double-edged sword with tumorigenesis and tumor prevention functions. Although micronuclei are small structures, the impact they have on cells and their microenvironment is quite large. Micronuclei, which contain faulty chromosomes or chromosome fragments and occur outside the main cellular nucleus, are prone to rupturing, which leads to DNA changes that can drive tumor development. A team led by Mijung Kwon from Ewha Womans University in Seoul and Jae-Ho Lee of Ajou University School of Medicine in Suwon, both in South Korea, review how these micronuclei tend to burst, spilling their contents into the cell with devastating consequences. The chromosomes they contain break into tiny fragments and this broken DNA finds its way into the main nucleus, leading to chromosomal rearrangements that can permanently alter genomic function. The rupture of micronuclei also activates a part of the innate immune system that can promote cancer cell invasion and spread. Drugs targeting these processes could aid in the treatment of cancer.
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影响因子：
4
作者：
Cimini, D;Moree, B;Salmon, ED
通讯作者：
Salmon, ED
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
DOI：
10.4161/nucl.23796
发表时间：
2013-03
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Clever M;Mimura Y;Funakoshi T;Imamoto N
通讯作者：
Imamoto N
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1126/science.1251121
发表时间：
2014-07-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Afonso O;Matos I;Pereira AJ;Aguiar P;Lampson MA;Maiato H
通讯作者：
Maiato H