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Cytokinesis-Block Micronucleus Cytome Assay Evolution into a More Comprehensive Method to Measure Chromosomal Instability
Genes ( IF 2.8 ) Pub Date : 2020-10-15 , DOI: 10.3390/genes11101203
Michael Fenech 1, 2, 3
Affiliation  

This review describes the cytokinesis-block micronucleus (CBMN) cytome assay and its evolution into a molecular cytogenetic method of chromosomal instability (CIN). Micronuclei (MNi) originate from whole chromosomes or chromosome fragments that fail to segregate to the poles of the cell during mitosis. These lagging chromosomes are excluded from the daughter nuclei and are enveloped in their own membrane to form MNi. The CBMN assay was developed to allow MNi to be scored exclusively in once-divided binucleated cells, which enables accurate measurement of chromosome breakage or loss without confounding by non-dividing cells that cannot express MNi. The CBMN assay can be applied to cell lines in vitro and cells such as lymphocytes that can be stimulated to divide ex vivo. In the CBMN assay, other CIN biomarkers such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are also measured. Use of centromere, telomere, and chromosome painting probes provides further insights into the mechanisms through which MNi, NPBs and NBUDs originate. Measurement of MNi is also important because entrapment within a micronucleus may cause chromosomes to shatter and, after nuclear reintegration, become rearranged. Additionally, leakage of DNA from MNi can stimulate inflammation via the cyclic GMP-AMP Synthase—Stimulator of Interferon Genes (cGAS-STING) DNA sensing mechanism of the innate immune system.

中文翻译:

细胞分裂-阻断微核细胞分析进化成更全面的方法来测量染色体不稳定性

这篇综述描述了胞质分裂阻断微核 (CBMN) 细胞组测定及其向染色体不稳定性 (CIN) 的分子细胞遗传学方法的演变。微核 (MNi) 源自整个染色体或染色体片段,它们在有丝分裂期间未能分离到细胞的两极。这些滞后的染色体被排除在子核之外,并被包裹在自己的膜中以形成 MNi。开发 CBMN 检测是为了让 MNi 仅在一次分裂的双核细胞中进行评分,从而能够准确测量染色体断裂或丢失,而不会被不能表达 MNi 的非分裂细胞混淆。CBMN 测定可应用于体外细胞系和可刺激体外分裂的淋巴细胞等细胞。在 CBMN 测定中,还测量了其他 CIN 生物标志物,例如核质桥 (NPB) 和核芽 (NBUD)。使用着丝粒、端粒和染色体着色探针可以进一步了解 MNi、NPB 和 NBUD 的起源机制。MNi 的测量也很重要,因为微核内的截留可能导致染色体破碎,并在核重新整合后重新排列。此外,从 MNi 泄漏的 DNA 可以通过先天免疫系统的环状 GMP-AMP 合酶 - 干扰素基因刺激剂 (cGAS-STING) DNA 传感机制刺激炎症。MNi 的测量也很重要,因为微核内的截留可能导致染色体破碎,并在核重新整合后重新排列。此外,从 MNi 泄漏的 DNA 可以通过先天免疫系统的环状 GMP-AMP 合酶 - 干扰素基因刺激剂 (cGAS-STING) DNA 传感机制刺激炎症。MNi 的测量也很重要,因为微核内的截留可能导致染色体破碎,并在核重新整合后重新排列。此外,从 MNi 泄漏的 DNA 可以通过先天免疫系统的环状 GMP-AMP 合酶 - 干扰素基因刺激剂 (cGAS-STING) DNA 传感机制刺激炎症。
更新日期:2020-10-15
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