Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA
| العنوان: | Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA |
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| المؤلفون: | Roy M. Golsteyn, Cody W. Lewis |
| المصدر: | Cell Cycle. 15:3131-3145 |
| بيانات النشر: | Informa UK Limited, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | DNA Replication, 0301 basic medicine, Biology, complex mixtures, Histones, 03 medical and health sciences, chemistry.chemical_compound, Report, Cell Line, Tumor, medicine, Humans, Cytotoxic T cell, DAPI, CHEK1, Molecular Biology, Mitosis, Micronuclei, Chromosome-Defective, Cisplatin, Chromothripsis, Cell Cycle Checkpoints, Glioma, Cell Biology, Molecular biology, 030104 developmental biology, chemistry, Cancer cell, Micronucleus test, DNA Damage, Signal Transduction, Developmental Biology, medicine.drug |
| الوصف: | We have examined the relationship between checkpoint adaptation (mitosis with damaged DNA) and micronuclei. Micronuclei in cancer cells are linked to genomic change, and may induce chromothripsis (chromosome shattering). We measured the cytotoxicity of the cancer drug cisplatin in M059K (glioma fibroblasts, IC50 15 μM). Nearly 100% of M059K cells were positive for histone γH2AX staining after 48 h treatment with a cytotoxic concentration of cisplatin. The proportion of micronucleated cells, as confirmed by microscopy using DAPI and lamin A/C staining, increased from 24% to 48%, and the total micronuclei in surviving cells accumulated over time. Promoting entry into mitosis with a checkpoint inhibitor increased the number of micronuclei in cells whereas blocking checkpoint adaptation with a Cdk inhibitor reduced the number of micronuclei. Interestingly, some micronuclei underwent asynchronous DNA replication, relative to the main nuclei, as measured by deoxy-bromo-uracil (BrdU) staining. These micronuclei stained positive for histone γH2AX, which was linked to DNA replication, suggesting that micronuclei arise from checkpoint adaptation and that micronuclei may continue to damage DNA. By contrast the normal cell line WI-38 did not undergo checkpoint adaptation when treated with cisplatin and did not show changes in micronuclei number. These data reveal that the production of micronuclei by checkpoint adaptation is part of a process that contributes to genomic change. |
| تدمد: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2016.1231287 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9c6e3010fabcd26adb1114f6ab8f425 https://doi.org/10.1080/15384101.2016.1231287 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d9c6e3010fabcd26adb1114f6ab8f425 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15514005 15384101 |
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| DOI: | 10.1080/15384101.2016.1231287 |