دورية أكاديمية
أعرض في EDS

DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.

التفاصيل البيبلوغرافية
العنوان: DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.
المؤلفون: Miron S; Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France., Legrand P; Synchrotron SOLEIL, HelioBio group, L'Orme des Merisiers, Gif sur-Yvette, France., Dupaigne P; Genome Maintenance and Molecular Microscopy UMR 9019 CNRS, Université Paris-Saclay, Gustave Roussy, Villejuif, France., van Rossum-Fikkert SE; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands., Ristic D; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands., Majeed A; Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France., Kanaar R; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands.; Oncode Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands., Zinn-Justin S; Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France., Zelensky AN; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands.; Oncode Institute, Erasmus University Medical Center, 3000CA, Rotterdam, The Netherlands.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Jul 08; Vol. 52 (12), pp. 7337-7353.
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: Rad51 Recombinase*/metabolism , Rad51 Recombinase*/genetics , Rad51 Recombinase*/chemistry , BRCA2 Protein*/metabolism , BRCA2 Protein*/chemistry , BRCA2 Protein*/genetics , Cell Cycle Proteins*/metabolism , Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/chemistry , DNA-Binding Proteins*/metabolism , DNA-Binding Proteins*/genetics , DNA-Binding Proteins*/chemistry , Protein Binding* , Amino Acid Motifs*, Animals ; Mice ; Humans ; Binding Sites ; Models, Molecular ; Crystallography, X-Ray ; Homologous Recombination ; Phosphate-Binding Proteins
مستخلص: In vertebrates, the BRCA2 protein is essential for meiotic and somatic homologous recombination due to its interaction with the RAD51 and DMC1 recombinases through FxxA and FxPP motifs (here named A- and P-motifs, respectively). The A-motifs present in the eight BRC repeats of BRCA2 compete with the A-motif of RAD51, which is responsible for its self-oligomerization. BRCs thus disrupt RAD51 nucleoprotein filaments in vitro. The role of the P-motifs is less studied. We recently found that deletion of Brca2 exons 12-14 encoding one of them (the prototypical 'PhePP' motif), disrupts DMC1 but not RAD51 function in mouse meiosis. Here we provide a mechanistic explanation for this phenotype by solving the crystal structure of the complex between a BRCA2 fragment containing the PhePP motif and DMC1. Our structure reveals that, despite sharing a conserved phenylalanine, the A- and P-motifs bind to distinct sites on the ATPase domain of the recombinases. The P-motif interacts with a site that is accessible in DMC1 octamers and nucleoprotein filaments. Moreover, we show that this interaction also involves the adjacent protomer and thus increases the stability of the DMC1 nucleoprotein filaments. We extend our analysis to other P-motifs from RAD51AP1 and FIGNL1.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: ANR-10-INSB-05-01 French Infrastructure for Integrated Structural Biology; 871037 European Community H2020; Institut National de la Santé et de la Recherche Médicale; Erasmus Medical Center; Dutch Cancer Society; Josephine Nefkens Cancer Program
المشرفين على المادة: EC 2.7.7.- (Rad51 Recombinase)
0 (BRCA2 Protein)
0 (Cell Cycle Proteins)
0 (DNA-Binding Proteins)
EC 3.6.1.- (DMC1 protein, human)
0 (BRCA2 protein, human)
0 (Dmc1 protein, mouse)
EC 2.7.7.- (Rad51 protein, mouse)
0 (Phosphate-Binding Proteins)
تواريخ الأحداث: Date Created: 20240603 Date Completed: 20240708 Latest Revision: 20240710
رمز التحديث: 20240710
مُعرف محوري في PubMed: PMC11229353
DOI: 10.1093/nar/gkae452
PMID: 38828772
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae452