RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery inCaenorhabditis elegans
| Autor: | Jorge Merlet, Batool Ossareh-Nazari, Lionel Pintard, Anthi Katsiarimpa |
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| Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), C.elegans Hérédité et Développement = C.elegans heredity and development (LBD-E03), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases DNA replication QH426-470 Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Genetics medicine Animals Genetic Testing Receptors Cytokine Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Gene Genetics (clinical) Mutation Cullin-RING E3-Ligases Mutant Screen Report Helicase Epistasis Genetic biology.organism_classification GINS 3. Good health DNA replication checkpoint Protein Subunits 030104 developmental biology Gene Expression Regulation Multiprotein Complexes C. elegans biology.protein Replisome RNA Interference 030217 neurology & neurosurgery |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 6, Iss 10, Pp 3431-3442 (2016) G3 G3, Genetics Society of America, 2016, 6 (10), pp.3431-3442. ⟨10.1534/g3.116.033043⟩ G3, 2016, 6 (10), pp.3431-3442. ⟨10.1534/g3.116.033043⟩ G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| DOI: | 10.1534/g3.116.033043 |
| Popis: | Cullin-RING E3-Ligases (CRLs), the largest family of E3 ubiquitin-Ligases, regulate diverse cellular processes by promoting ubiquitination of target proteins. The evolutionarily conserved Leucine Rich Repeat protein 1 (LRR-1) is a substrate-recognition subunit of a CRL2LRR-1 E3-ligase. Here we provide genetic evidence supporting a role of this E3-enzyme in the maintenance of DNA replication integrity in Caenorhabditis elegans. Through RNAi-based suppressor screens of lrr-1(0) and cul-2(or209ts) mutants, we identified two genes encoding components of the GINS complex, which is part of the Cdc45-MCM-GINS (CMG) replicative helicase, as well as CDC-7 and MUS-101, which drives the assembly of the CMG helicase during DNA replication. In addition, we identified the core components of the ATR/ATL-1 DNA replication checkpoint pathway (MUS-101, ATL-1, CLSP-1, CHK-1). These results suggest that the CRL2LRR-1 E3-ligase acts to modify or degrade factor(s) that would otherwise misregulate the replisome, eventually leading to the activation of the DNA replication checkpoint. |
| Databáze: | OpenAIRE |
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