MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair
| Autor: | de Krijger, Inge, Föhr, Bastian, Pérez, Santiago Hernández, Vincendeau, Estelle, Serrat, Judit, Thouin, Alexander Marc, Susvirkar, Vivek, Lescale, Chloé, Paniagua, Inés, Hoekman, Liesbeth, Kaur, Simranjeet, Altelaar, Maarten, Deriano, Ludovic, Faesen, Alex C, Jacobs, Jacqueline J L, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics |
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| Přispěvatelé: | Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University [Utrecht], This work was supported by project grant 10999/2017-1 from the Dutch Cancer Society (KWF) to J.J.L.J., by the Institut Pasteur to L.D., by the Institut National Du Cancer (INCA_13852) to L.D., by the Ligue Nationale Contre le Cancer (Equipe labellisée 2019) to L.D. The Proteomics Facility of the Netherlands Cancer Institute was supported by the X-omics Initiative, partially funded by the Dutch Research Council (NWO)(project 184.034.019). E.V. received funding from Université de Paris, Sorbonne Paris Cité. A.C.F. is grateful for generous core funding by the Max Planck Society., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Sorbonne Paris Cité (USPC), Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Lescale, Chloé |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DNA Repair
Chemistry(all) ATPase MESH: DNA Breaks Double-Stranded Gene Expression General Physics and Astronomy Cell Cycle Proteins [SDV.GEN] Life Sciences [q-bio]/Genetics [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biochemistry Piperazines MESH: Recombinant Proteins Mice chemistry.chemical_compound 0302 clinical medicine DNA Breaks Double-Stranded MESH: Animals 0303 health sciences Multidisciplinary biology Chemistry MESH: Protein Multimerization DNA damage and repair MESH: DNA Recombinant Proteins 3. Good health Cell biology DNA-Binding Proteins MESH: ATPases Associated with Diverse Cellular Activities MESH: HEK293 Cells Mad2 Proteins MESH: Phthalazines MESH: Mad2 Proteins Protein Binding MESH: Cell Line Tumor MESH: Gene Expression DNA repair Science Physics and Astronomy(all) Article Chromosomes General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences MESH: Cell Cycle Proteins Cell Line Tumor Animals Humans MESH: Protein Binding Protein Interaction Domains and Motifs MESH: Mice 030304 developmental biology MESH: Protein Interaction Domains and Motifs [SDV.GEN]Life Sciences [q-bio]/Genetics Binding Sites MESH: Humans TRIP13 Biochemistry Genetics and Molecular Biology(all) [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology DNA General Chemistry DNA Repair Pathway Fibroblasts MESH: Cell Line HEK293 Cells MESH: Binding Sites MESH: Cisplatin MESH: Fibroblasts MESH: HeLa Cells biology.protein ATPases Associated with Diverse Cellular Activities Phthalazines Cisplatin Protein Multimerization 030217 neurology & neurosurgery Function (biology) MESH: DNA-Binding Proteins HeLa Cells Genetics and Molecular Biology(all) |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.5421. ⟨10.1038/s41467-021-25724-y⟩ Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications, 12(1). Nature Publishing Group Nature Communications, 2021, 12 (1), pp.5421. ⟨10.1038/s41467-021-25724-y⟩ Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-25724-y⟩ |
| ISSN: | 2041-1723 |
| Popis: | MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting of MAD2L2, SHLD1, SHLD2 and SHLD3, it controls DNA repair pathway choice by counteracting DNA end-resection. Here we investigated the requirements for shieldin complex assembly and activity. Besides a dimerization-surface, HORMA-domain protein MAD2L2 has the extraordinary ability to wrap its C-terminus around SHLD3, likely creating a very stable complex. We show that appropriate function of MAD2L2 within shieldin requires its dimerization, mediated by SHLD2 and accelerating MAD2L2-SHLD3 interaction. Dimerization-defective MAD2L2 impairs shieldin assembly and fails to promote NHEJ. Moreover, MAD2L2 dimerization, along with the presence of SHLD3, allows shieldin to interact with the TRIP13 ATPase, known to drive topological switches in HORMA-domain proteins. We find that appropriate levels of TRIP13 are important for proper shieldin (dis)assembly and activity in DNA repair. Together our data provide important insights in the dependencies for shieldin activity. MAD2L2 — a member of the shieldin complex — is known to play important roles in DNA repair. Here the authors demonstrate how MAD2L2 dimerization mediated through SHLD2 participates in shieldin assembly and function. |
| Databáze: | OpenAIRE |
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