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微核中的遗传活性:被困在微核中的 DNA 是否会被细胞丢失?

Genetic activities in micronuclei: is the DNA entrapped in micronuclei lost for the cell?

机构信息

Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

出版信息

Mutat Res. 2010 Jul-Sep;705(1):60-7. doi: 10.1016/j.mrrev.2010.03.004. Epub 2010 Mar 20.

DOI:10.1016/j.mrrev.2010.03.004
PMID:20307686
Abstract

Micronuclei are good markers of genotoxic exposure in humans and their scoring has been extensively used to identify potential genotoxic agents. Micronuclei are also indicators of chromosomal instability, since the frequency of micronuclei is higher in tumour cells and cells with a defective DNA damage repair system or disrupted cell cycle checkpoint machinery. Despite the widespread use of this biomarker, information on the basic biology of micronuclei and the impact of micronuclei on the cell is relatively controversial. In some cell systems, micronuclei are considered to be genetic material that is lost for the cell; whereas other studies suggest that micronuclear DNA is actively transcribed and its genes are fully expressed. Recently, evidence has accumulated suggesting that damaged DNA entrapped in micronuclei induces a defective cell cycle checkpoint arrest and DNA repair response, and that micronuclear content can be degraded without inducing an immediate cell cycle arrest or causing the cell to enter apoptosis. Overall, these findings emphasise the important consequences of micronucleus formation in terms of chromosomal instability in general and gene loss in particular.

摘要

微核是人类遗传毒性暴露的良好标志物,其评分已被广泛用于识别潜在的遗传毒性剂。微核也是染色体不稳定性的指标,因为肿瘤细胞和具有缺陷的 DNA 损伤修复系统或破坏的细胞周期检查点机制的细胞中的微核频率更高。尽管该生物标志物得到了广泛应用,但有关微核的基本生物学和微核对细胞的影响的信息仍存在争议。在一些细胞系统中,微核被认为是细胞丢失的遗传物质;而其他研究表明,微核 DNA 是被积极转录的,其基因是完全表达的。最近,有证据表明,被困在微核中的受损 DNA 会导致细胞周期检查点阻滞和 DNA 修复反应缺陷,并且微核内容物可以降解而不会立即引起细胞周期阻滞或导致细胞进入凋亡。总的来说,这些发现强调了微核形成在染色体不稳定性特别是基因丢失方面的重要后果。

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