Dun1, a Chk2-related kinase, is the central regulator of securin-separase dynamics during DNA damage signaling
| العنوان: | Dun1, a Chk2-related kinase, is the central regulator of securin-separase dynamics during DNA damage signaling |
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| المؤلفون: | Idina Shi, Candice Qiu Xia Yam, Hong Hwa Lim, David Boy Chia, Uttam Surana |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | G2 Phase, Saccharomyces cerevisiae Proteins, Cell cycle checkpoint, DNA Repair, Transcription, Genetic, AcademicSubjects/SCI00010, DNA repair, DNA damage, Mitosis, Cell Cycle Proteins, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Biology, Anaphase-Promoting Complex-Cyclosome, 03 medical and health sciences, Chromosome Segregation, Genetics, Molecular Biology, Separase, 030304 developmental biology, 0303 health sciences, Endosomal Sorting Complexes Required for Transport, 030302 biochemistry & molecular biology, Ubiquitin-Protein Ligase Complexes, Cell Cycle Checkpoints, G2-M DNA damage checkpoint, Cell biology, Securin, Checkpoint Kinase 2, Proteolysis, biological phenomena, cell phenomena, and immunity, Anaphase-promoting complex, Gene Deletion, DNA Damage, Signal Transduction |
| الوصف: | The DNA damage checkpoint halts cell cycle progression in G2 in response to genotoxic insults. Central to the execution of cell cycle arrest is the checkpoint-induced stabilization of securin-separase complex (yeast Pds1-Esp1). The checkpoint kinases Chk1 and Chk2 (yeast Chk1 and Rad53) are thought to critically contribute to the stability of securin-separase complex by phosphorylation of securin, rendering it resistant to proteolytic destruction by the anaphase promoting complex (APC). Dun1, a Rad53 paralog related to Chk2, is also essential for checkpoint-imposed arrest. Dun1 is required for the DNA damage-induced transcription of DNA repair genes; however, its role in the execution of cell cycle arrest remains unknown. Here, we show that Dun1′s role in checkpoint arrest is independent of its involvement in the transcription of repair genes. Instead, Dun1 is necessary to prevent Pds1 destruction during DNA damage in that the Dun1-deficient cells degrade Pds1, escape G2 arrest and undergo mitosis despite the presence of checkpoint-active Chk1 and Rad53. Interestingly, proteolytic degradation of Pds1 in the absence of Dun1 is mediated not by APC but by the HECT domain-containing E3 ligase Rsp5. Our results suggest a regulatory scheme in which Dun1 prevents chromosome segregation during DNA damage by inhibiting Rsp5-mediated proteolytic degradation of securin Pds1. |
| تدمد: | 1362-4962 0305-1048 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e041a4167b7a1c58a41e492a7eaf456Test https://doi.org/10.1093/nar/gkaa355Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9e041a4167b7a1c58a41e492a7eaf456 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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