Academic Journal
Abstract 289: The key role of Mitostatin in the maintenance of genome stability
| العنوان: | Abstract 289: The key role of Mitostatin in the maintenance of genome stability |
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| المؤلفون: | Lauriola, Angela, Caporali, Andrea, Mai, Sabine, D'Arca, Domenico |
| المساهمون: | Lauriola, Angela, Caporali, Andrea, Mai, Sabine, D'Arca, Domenico |
| سنة النشر: | 2017 |
| المجموعة: | Università degli Studi di Verona: Catalogo dei Prodotti della Ricerca (IRIS) |
| مصطلحات موضوعية: | DNA damage, Mad2, cancer, chromosome instability, chromosome mis-segregation, mitostatin, spectral karyotyping (SKY), spindle assembly checkpoint (SAC) |
| الوصف: | Genomic instability is a characteristic of most cancers and it refers to an increased tendency of alterations in the genome during the life cycle of cells. The fidelity of DNA replication is highly ensured by different checkpoints; the activation of spindle checkpoints prevents cells from premature entry into mitosis, avoiding incorrect chromosome segregation and aneuploidy, a typical feature of many cancers. Mitostatin, a novel protein, endowed with tumor suppressor activity, has been reported to bind centrosomal proteins Odf2 and ninein, and its depletion causes an alteration of the anchorage of microtubules to the centrosome. Since functional defects of centrosomes are associated to mitotic failure, Mitostatin may have a key role in guarding the fidelity of mitosis in cells.Here we show that the depletion of Mitostatin in cancer cells, synchronized by aphidicolin (G1/S) block and released into nocodazole-containing medium, leads to mitotic slippage and adaptation to the spindle checkpoint in the presence of a spindle inhibitor. Concomitantly, Mitostatin depletion promotes the early degradation of Mad2 and cyclin B1. Since the activated spindle checkpoint delays cell exit from mitosis by preventing cyclin B1 proteolysis, the cyclin B1 early degradation leads to mitotic checkpoint escape and resulting chromosome instability. In particular, we observed a premature sister-chromatid separation, chromosome bridges and mis-segregation in anaphase that are consistent with defective activation of the spindle checkpoint.In this study, we report for the first time that the depletion of Mitostatin induces an increase of numerical and structural chromosomal aberrations compared to control cells. These aberrations include aneuploidy (P=.0005), the formation of triradials (P=.0061) and broken chromosomes (P=.0066). Moreover, 3D nuclear telomere analysis using TeloView shows decreases in telomeric signals (P=.0061), in the total number of aggregates (P=.0027), and in total intensity (P=.018) and single intensity (P=.019) in ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000442496701283; volume:77; issue:13_Supplement; firstpage:289; lastpage:289; numberofpages:1; journal:CANCER RESEARCH; https://hdl.handle.net/11562/1129869; https://aacrjournals.org/cancerres/article/77/13_Supplement/289/618448/Abstract-289-The-key-role-of-Mitostatin-in-the |
| DOI: | 10.1158/1538-7445.am2017-289 |
| الاتاحة: | https://hdl.handle.net/11562/1129869 https://doi.org/10.1158/1538-7445.am2017-289 https://aacrjournals.org/cancerres/article/77/13_Supplement/289/618448/Abstract-289-The-key-role-of-Mitostatin-in-the |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D936D355 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/1538-7445.am2017-289 |
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