دورية أكاديمية

Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.

التفاصيل البيبلوغرافية
العنوان: Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.
المؤلفون: Olsen JG; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Prestel A; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Kassem N; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Broendum SS; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Shamim HM; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Simonsen S; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Grysbæk M; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Mortensen J; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Rytkjær LL; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Haxholm GW; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Marabini R; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Holmberg C; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Carr AM; Genome Damage and Stability Centre, University of Sussex, John Maynard Smith Building, Falmer, BN1 9RQ, Brighton., Crehuet R; Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, c/ Jordi Girona 18-26, 08034 Barcelona., Nielsen O; Cell cycle and Genome Stability Group, Functional Genomics, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark., Kragelund BB; Structural Biology and NMR Laboratory, The Linderstrøm-Lang Centre for Protein Science and REPIN, Department of Biology, Ole Maaloes Vej 5, University of Copenhagen, 2200 Copenhagen N, Denmark.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Feb 28; Vol. 52 (4), pp. 2030-2044.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Proliferating Cell Nuclear Antigen*/metabolism , Schizosaccharomyces pombe Proteins*/chemistry , Schizosaccharomyces pombe Proteins*/metabolism , Cell Cycle Proteins*/chemistry , Cell Cycle Proteins*/metabolism, Binding Sites ; DNA Replication ; Intrinsically Disordered Proteins/chemistry ; Protein Binding ; Ribonucleotide Reductases/genetics ; Schizosaccharomyces/genetics
مستخلص: DNA regulation, replication and repair are processes fundamental to all known organisms and the sliding clamp proliferating cell nuclear antigen (PCNA) is central to all these processes. S-phase delaying protein 1 (Spd1) from S. pombe, an intrinsically disordered protein that causes checkpoint activation by inhibiting the enzyme ribonucleotide reductase, has one of the most divergent PCNA binding motifs known. Using NMR spectroscopy, in vivo assays, X-ray crystallography, calorimetry, and Monte Carlo simulations, an additional PCNA binding motif in Spd1, a PIP-box, is revealed. The two tandemly positioned, low affinity sites exchange rapidly on PCNA exploiting the same binding sites. Increasing or decreasing the binding affinity between Spd1 and PCNA through mutations of either motif compromised the ability of Spd1 to cause checkpoint activation in yeast. These results pinpoint a role for PCNA in Spd1-mediated checkpoint activation and suggest that its tandemly positioned short linear motifs create a neatly balanced competition-based system, involving PCNA, Spd1 and the small ribonucleotide reductase subunit, Suc22R2. Similar mechanisms may be relevant in other PCNA binding ligands where divergent binding motifs so far have gone under the PIP-box radar.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: 12-1118 AICR; 4181-00344 Danish Council for Independent Research Natural Sciences; NNF18OC0033926 Novo Nordisk Foundation; Thrond Mohn stiftelsen (TAMiR project); European Synchrotron Radiation Facility; Structural Biology and NMR Laboratory; Villumfonden; Carlsberg Foundation; Novo Nordisk Scholarship
المشرفين على المادة: 0 (Intrinsically Disordered Proteins)
0 (Proliferating Cell Nuclear Antigen)
EC 1.17.4.- (Ribonucleotide Reductases)
0 (Spd1 protein, S pombe)
0 (Schizosaccharomyces pombe Proteins)
0 (Cell Cycle Proteins)
تواريخ الأحداث: Date Created: 20240123 Date Completed: 20240229 Latest Revision: 20240316
رمز التحديث: 20240316
مُعرف محوري في PubMed: PMC10939359
DOI: 10.1093/nar/gkae011
PMID: 38261971
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae011