Antagonistic control of DDK binding to licensed replication origins by Mcm2 and Rad53
| العنوان: | Antagonistic control of DDK binding to licensed replication origins by Mcm2 and Rad53 |
|---|---|
| المؤلفون: | Dirk Remus, Syafiq Abd Wahab |
| المصدر: | eLife, Vol 9 (2020) eLife |
| بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Saccharomyces cerevisiae Proteins, QH301-705.5, Science, DDK, Chemical biology, S. cerevisiae, Cell Cycle Proteins, Replication Origin, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, DNA replication, Origin of replication, General Biochemistry, Genetics and Molecular Biology, chemistry.chemical_compound, checkpoint, Protein Domains, Biochemistry and Chemical Biology, Kinase activity, Biology (General), DNA, Fungal, General Immunology and Microbiology, biology, Kinase, General Neuroscience, Helicase, General Medicine, Chromosomes and Gene Expression, Cell biology, Mcm2-7, Checkpoint Kinase 2, chemistry, Rad53, biology.protein, Phosphorylation, Medicine, Function (biology), DNA, Protein Binding, Research Article |
| الوصف: | Eukaryotic replication origins are licensed by the loading of the replicative DNA helicase, Mcm2-7, in inactive double hexameric form around DNA. Subsequent origin activation is under control of multiple protein kinases that either promote or inhibit origin activation, which is important for genome maintenance. Using the reconstituted budding yeast DNA replication system, we find that the flexible N-terminal tail of Mcm2 promotes the stable recruitment of Dbf4-dependent kinase (DDK) to Mcm2-7 double hexamers, which in turn promotes DDK phosphorylation of Mcm4 and -6 and subsequent origin activation. Conversely, we demonstrate that the checkpoint kinase, Rad53, inhibits DDK binding to Mcm2-7 double hexamers. Unexpectedly, this function is not dependent on Rad53 kinase activity, but requires Rad53 activation by trans-autophosphorylation, suggesting steric inhibition of DDK by activated Rad53. These findings identify critical determinants of the origin activation reaction and uncover a novel mechanism for checkpoint-dependent origin inhibition. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e21c1eba431a2132fa060498c22cc57Test https://elifesciences.org/articles/58571Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e21c1eba431a2132fa060498c22cc57 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |