Mitotic entry upon Topo II catalytic inhibition is controlled by Chk1 and Plk1
| العنوان: | Mitotic entry upon Topo II catalytic inhibition is controlled by Chk1 and Plk1 |
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| المؤلفون: | Florian D. Hastert, Ana Cañuelo, J. Alberto Marchal, María Arroyo, Antonio Sánchez, Jesús Calahorra, Duncan J. Clarke |
| المصدر: | FEBS J |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Immunoblotting, Regulator, Mitosis, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biochemistry, PLK1, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, Humans, Topoisomerase II Inhibitors, CHEK1, Molecular Biology, Loss function, biology, Chemistry, Kinase, Topoisomerase, Cell Biology, G2-M DNA damage checkpoint, Flow Cytometry, Cell biology, G2 Phase Cell Cycle Checkpoints, Cytoskeletal Proteins, DNA Topoisomerases, Type II, HEK293 Cells, 030104 developmental biology, 030220 oncology & carcinogenesis, Checkpoint Kinase 1, Biocatalysis, biology.protein, biological phenomena, cell phenomena, and immunity, HeLa Cells |
| الوصف: | Catalytic inhibition of topoisomerase II during G2 phase delays onset of mitosis due to the activation of the so-called decatenation checkpoint. This checkpoint is less known compared with the extensively studied G2 DNA damage checkpoint and is partially compromised in many tumor cells. We recently identified MCPH1 as a key regulator that confers cells with the capacity to adapt to the decatenation checkpoint. In the present work, we have explored the contributions of checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1), in order to better understand the molecular basis of decatenation checkpoint. Our results demonstrate that Chk1 function is required to sustain the G2 arrest induced by catalytic inhibition of Topo II. Interestingly, Chk1 loss of function restores adaptation in cells lacking MCPH1. Furthermore, we demonstrate that Plk1 function is required to bypass the decatenation checkpoint arrest in cells following Chk1 inhibition. Taken together, our data suggest that MCPH1 is critical to allow checkpoint adaptation by counteracting Chk1-mediated inactivation of Plk1. Importantly, we also provide evidence that MCPH1 function is not required to allow recovery from this checkpoint, which lends support to the notion that checkpoint adaptation and recovery are different mechanisms distinguished in part by specific effectors. |
| تدمد: | 1742-4658 1742-464X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97240d987ac698c05774c1c430750b8aTest https://doi.org/10.1111/febs.15280Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....97240d987ac698c05774c1c430750b8a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424658 1742464X |
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