The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
| Autor: | Virginie Boucherit, Catherine H. Freudenreich, Benoit Palancade, Sarah Lambert, Anissia Ait Saada, Karol Kramarz, Kamila Schirmeisen, Claire Lovo |
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| Přispěvatelé: | Intégrité du génome, ARN et cancer, Institut Curie [Paris]-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Tufts University [Medford] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genome instability Genomic instability DNA Replication Cell biology Proteasome Endopeptidase Complex Transcription Genetic DNA repair Molecular biology Science [SDV]Life Sciences [q-bio] RAD51 General Physics and Astronomy Microbiology General Biochemistry Genetics and Molecular Biology Article Ligases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Schizosaccharomyces Genetics Nuclear pore lcsh:Science Recombination Genetic Multidisciplinary DNA synthesis Chemistry General Chemistry 030104 developmental biology Proteasome Nuclear Pore Small Ubiquitin-Related Modifier Proteins lcsh:Q Schizosaccharomyces pombe Proteins Homologous recombination 030217 neurology & neurosurgery DNA |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-020-19516-z⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-19516-z⟩ |
| Popis: | Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and generates poly-SUMOylation which promote relocation to NPCs but impede the resumption of DNA synthesis by homologous recombination (HR). Anchorage to NPCs allows SUMO removal by the SENP SUMO protease Ulp1 and the proteasome, promoting timely resumption of DNA synthesis. Preventing Pli1-mediated SUMO chains was sufficient to bypass the need for anchorage to NPCs and the inhibitory effect of poly-SUMOylation on HR-mediated DNA synthesis. Our work establishes a novel spatial control of Recombination-Dependent Replication (RDR) at a unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences. In yeast, collapsed forks shift to the nuclear periphery to associate with two distinct perinuclear anchorage sites such as the nuclear pore complex. Here, the authors reveal the mechanisms engaged at nuclear pore complex facilitating fork integrity and restart via SUMO regulation. |
| Databáze: | OpenAIRE |
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