دورية أكاديمية
أعرض في EDS

A conserved mechanism for regulating replisome disassembly in eukaryotes.

التفاصيل البيبلوغرافية
العنوان: A conserved mechanism for regulating replisome disassembly in eukaryotes.
المؤلفون: Jenkyn-Bedford M; MRC Laboratory of Molecular Biology, Cambridge, UK., Jones ML; MRC Laboratory of Molecular Biology, Cambridge, UK., Baris Y; MRC Laboratory of Molecular Biology, Cambridge, UK., Labib KPM; MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, UK., Cannone G; MRC Laboratory of Molecular Biology, Cambridge, UK., Yeeles JTP; MRC Laboratory of Molecular Biology, Cambridge, UK. jyeeles@mrc-lmb.cam.ac.uk., Deegan TD; MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, UK. tdeegan@ed.ac.uk.; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK. tdeegan@ed.ac.uk.
المصدر: Nature [Nature] 2021 Dec; Vol. 600 (7890), pp. 743-747. Date of Electronic Publication: 2021 Oct 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: DNA Replication* , Eukaryota*/genetics, Cryoelectron Microscopy ; DNA/metabolism ; DNA Helicases/metabolism ; Humans ; Ubiquitin-Protein Ligases/metabolism
مستخلص: Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase 1-3 . Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCF Dia2 in budding yeast 1 , CUL2 LRR1 in metazoa 4-7 ), replisome disassembly is governed by a common regulatory principle, in which ubiquitylation of CMG is suppressed before replication termination, to prevent replication fork collapse. Recent evidence suggests that this suppression is mediated by replication fork DNA 8-10 . However, it is unknown how SCF Dia2 and CUL2 LRR1 discriminate terminated from elongating replisomes, to selectively ubiquitylate CMG only after termination. Here we used cryo-electron microscopy to solve high-resolution structures of budding yeast and human replisome-E3 ligase assemblies. Our structures show that the leucine-rich repeat domains of Dia2 and LRR1 are structurally distinct, but bind to a common site on CMG, including the MCM3 and MCM5 zinc-finger domains. The LRR-MCM interaction is essential for replisome disassembly and, crucially, is occluded by the excluded DNA strand at replication forks, establishing the structural basis for the suppression of CMG ubiquitylation before termination. Our results elucidate a conserved mechanism for the regulation of replisome disassembly in eukaryotes, and reveal a previously unanticipated role for DNA in preserving replisome integrity.
(© 2021. The Author(s).)
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معلومات مُعتمدة: 24558 United Kingdom CRUK_ Cancer Research UK; MC_U105184326 United Kingdom MRC_ Medical Research Council; MC_UP_1201/12 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_UU_00018/4 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 9007-49-2 (DNA)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 3.6.4.- (DNA Helicases)
تواريخ الأحداث: Date Created: 20211026 Date Completed: 20220419 Latest Revision: 20240313
رمز التحديث: 20240313
مُعرف محوري في PubMed: PMC8695382
DOI: 10.1038/s41586-021-04145-3
PMID: 34700328
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-021-04145-3