دورية أكاديمية
DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in Caenorhabditis elegans .
العنوان: | DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in Caenorhabditis elegans . |
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المؤلفون: | Xia Y; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK., Sonneville R; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK., Jenkyn-Bedford M; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK., Ji L; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China., Alabert C; Division of Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, UK., Hong Y; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK.; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China., Yeeles JTP; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK., Labib KPM; The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK. |
المصدر: | Science (New York, N.Y.) [Science] 2023 Sep 22; Vol. 381 (6664), pp. eadi4932. Date of Electronic Publication: 2023 Sep 22. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
مواضيع طبية MeSH: | Caenorhabditis elegans*/genetics , Caenorhabditis elegans*/metabolism , DNA Replication* , Minichromosome Maintenance Proteins*/chemistry , Minichromosome Maintenance Proteins*/genetics , Minichromosome Maintenance Proteins*/metabolism , Caenorhabditis elegans Proteins*/chemistry , Caenorhabditis elegans Proteins*/genetics , Caenorhabditis elegans Proteins*/metabolism, Animals ; Cell Cycle Proteins/metabolism ; Cryoelectron Microscopy ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Protein Domains |
مستخلص: | Assembly of the CMG (CDC-45-MCM-2-7-GINS) helicase is the key regulated step during eukaryotic DNA replication initiation. Until now, it was unclear whether metazoa require additional factors that are not present in yeast. In this work, we show that Caenorhabditis elegans DNSN-1, the ortholog of human DONSON, functions during helicase assembly in a complex with MUS-101/TOPBP1. DNSN-1 is required to recruit the GINS complex to chromatin, and a cryo-electron microscopy structure indicates that DNSN-1 positions GINS on the MCM-2-7 helicase motor (comprising the six MCM-2 to MCM-7 proteins), by direct binding of DNSN-1 to GINS and MCM-3, using interfaces that we show are important for initiation and essential for viability. These findings identify DNSN-1 as a missing link in our understanding of DNA replication initiation, suggesting that initiation defects underlie the human disease syndrome that results from DONSON mutations. |
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معلومات مُعتمدة: | 24558 United Kingdom CRUK_ Cancer Research UK; MC_UU_12016/13 United Kingdom MRC_ Medical Research Council; MC_UP_1201/12 United Kingdom MRC_ Medical Research Council; 21782 United Kingdom CRUK_ Cancer Research UK; MC_UU_00018/4 United Kingdom MRC_ Medical Research Council |
المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (evl-18 protein, C elegans) EC 3.6.4.12 (Minichromosome Maintenance Proteins) 0 (Caenorhabditis elegans Proteins) 0 (Chromosomal Proteins, Non-Histone) |
تواريخ الأحداث: | Date Created: 20230817 Date Completed: 20230926 Latest Revision: 20240313 |
رمز التحديث: | 20240313 |
مُعرف محوري في PubMed: | PMC7615117 |
DOI: | 10.1126/science.adi4932 |
PMID: | 37590372 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1095-9203 |
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DOI: | 10.1126/science.adi4932 |