دورية أكاديمية
RNF8-mediated multi-ubiquitination of MCM7: Linking disassembly of the CMG helicase with DNA damage response in human cells.
| العنوان: | RNF8-mediated multi-ubiquitination of MCM7: Linking disassembly of the CMG helicase with DNA damage response in human cells. |
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| المؤلفون: | Sun Q; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 10005, China., Sui Y; School of Life Sciences, Chongqing University; Chongqing 401331, China., Li S; School of Life Sciences, Chongqing University; Chongqing 401331, China., Zhou R; School of Life Sciences, Chongqing University; Chongqing 401331, China., Fu Z; School of Life Sciences, Chongqing University; Chongqing 401331, China., Luo J; School of Life Sciences, Chongqing University; Chongqing 401331, China., Zhao W; School of Life Sciences, Chongqing University; Chongqing 401331, China. Electronic address: zhaowenhui@cqu.edu.cn. |
| المصدر: | Life sciences [Life Sci] 2024 Sep 15; Vol. 353, pp. 122912. Date of Electronic Publication: 2024 Jul 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Ubiquitin-Protein Ligases*/metabolism , Ubiquitin-Protein Ligases*/genetics , Ubiquitination* , DNA Damage* , Minichromosome Maintenance Complex Component 7*/metabolism , Minichromosome Maintenance Complex Component 7*/genetics , DNA-Binding Proteins*/metabolism , DNA-Binding Proteins*/genetics , DNA Replication*, Humans ; BRCA1 Protein/metabolism ; BRCA1 Protein/genetics ; HEK293 Cells ; DNA Repair ; HeLa Cells |
| مستخلص: | DNA damage causes genomic instability. To maintain genome integrity, cells have evolved DNA damage response, which is involved in replication fork disassembly and DNA replication termination. However, the mechanism underlying the regulation of replication fork disassembly and its connection with DNA damage repair remain elusive. The CMG-MCM7 subunit ubiquitination functions on the eukaryotic replication fork disassembly at replication termination. Until now, only ubiquitin ligases CUL2 LRR1 have been reported catalyzing MCM7 ubiquitination in human cells. This study discovered that in human cells, the ubiquitin ligase RNF8 catalyzes K63-linked multi-ubiquitination of MCM7 at K145 both in vivo and in vitro. The multi-ubiquitination of MCM7 is dynamically regulated during the cell cycle, primarily presenting on chromatin during the late S phase. Additionally, MCM7 polyubiquitylation is promoted by RNF168 and BRCA1 during DNA replication termination. Upon DNA damage, the RNF8-mediated polyubiquitination of MCM7 decreased significantly during the late S phase. This study highlights the novel role of RNF8-catalyzed polyubiquitination of MCM7 in the regulation of replication fork disassembly in human cells and linking it to DNA damage response. Competing Interests: Declaration of competing interest All authors listed have contributed significantly and take public responsibility for the appropriateness of the experimental design and method, and the collection, analysis, and interpretation of the data. The authors have reviewed the final version of the manuscript and approved it for publication. The authors also declare that they have no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CMG helicase; DNA damage response; MCM7; Ubiquitin ligase RNF8; Ubiquitination |
| المشرفين على المادة: | EC 2.3.2.27 (Ubiquitin-Protein Ligases) 0 (RNF8 protein, human) EC 3.6.4.12 (Minichromosome Maintenance Complex Component 7) 0 (DNA-Binding Proteins) EC 3.6.4.12 (MCM7 protein, human) 0 (BRCA1 Protein) 0 (BRCA1 protein, human) EC 2.3.2.27 (RNF168 protein, human) |
| تواريخ الأحداث: | Date Created: 20240714 Date Completed: 20240815 Latest Revision: 20240815 |
| رمز التحديث: | 20240816 |
| DOI: | 10.1016/j.lfs.2024.122912 |
| PMID: | 39004272 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
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| DOI: | 10.1016/j.lfs.2024.122912 |