Shared and distinct roles of Esc2 and Mms21 in suppressing genome rearrangements and regulating intracellular sumoylation
| العنوان: | Shared and distinct roles of Esc2 and Mms21 in suppressing genome rearrangements and regulating intracellular sumoylation |
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| المؤلفون: | Pang-Che Wang, Yong-Qi Gao, Huilin Zhou, Ann L. Zhou, Yusheng Yang, Raymond T. Suhandynata |
| المصدر: | PLoS ONE, Vol 16, Iss 2, p e0247132 (2021) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, SUMO protein, Cell Cycle Proteins, Yeast and Fungal Models, medicine.disease_cause, Biochemistry, Ligases, Schizosaccharomyces Pombe, 0302 clinical medicine, 0303 health sciences, Mutation, Multidisciplinary, biology, Protein Stability, Chemistry, Eukaryota, Enzymes, Cell biology, Ubiquitin ligase, Nucleic acids, Experimental Organism Systems, Cell Processes, Medicine, Post-translational modification, Protein Binding, Research Article, DNA Replication, Protein sumoylation, Saccharomyces cerevisiae Proteins, DNA damage, DNA repair, Ubiquitin-Protein Ligases, Science, SUMO-1 Protein, Down-Regulation, Saccharomyces cerevisiae, Research and Analysis Methods, Cell Growth, Saccharomyces, 03 medical and health sciences, Model Organisms, Protein Domains, Schizosaccharomyces, Genetics, medicine, Amino Acid Sequence, 030304 developmental biology, Biology and life sciences, Organisms, Fungi, DNA replication, Sumoylation, Proteins, Helicase, DNA, Cell Biology, Yeast, Mutagenesis, Ubiquitin-Conjugating Enzymes, Enzymology, Animal Studies, biology.protein, Sequence Alignment, 030217 neurology & neurosurgery, DNA Damage |
| الوصف: | Protein sumoylation, especially when catalyzed by the Mms21 SUMO E3 ligase, plays a major role in suppressing duplication-mediated gross chromosomal rearrangements (dGCRs). How Mms21 targets its substrates in the cell is insufficiently understood. Here, we demonstrate that Esc2, a protein with SUMO-like domains (SLDs), recruits the Ubc9 SUMO conjugating enzyme to specifically facilitate Mms21-dependent sumoylation and suppress dGCRs. The D430R mutation in Esc2 impairs its binding to Ubc9 and causes a synergistic growth defect and accumulation of dGCRs with mutations that delete the Siz1 and Siz2 E3 ligases. By contrast, esc2-D430R does not appreciably affect sensitivity to DNA damage or the dGCRs caused by the catalytically inactive mms21-CH. Moreover, proteome-wide analysis of intracellular sumoylation demonstrates that esc2-D430R specifically down-regulates sumoylation levels of Mms21-preferred targets, including the nucleolar proteins, components of the SMC complexes and the MCM complex that acts as the catalytic core of the replicative DNA helicase. These effects closely resemble those caused by mms21-CH, and are relatively unaffected by deleting Siz1 and Siz2. Thus, by recruiting Ubc9, Esc2 facilitates Mms21-dependent sumoylation to suppress the accumulation of dGCRs independent of Siz1 and Siz2. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd739b4bca0b7e377421521c74918bdf https://doi.org/10.1371/journal.pone.0247132 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dd739b4bca0b7e377421521c74918bdf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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