title: RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans.
abstract: 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-1E3-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-1E3-ligase acts to modify or degrade factor(s) that would otherwise misregulate the replisome, eventually leading to the activation of the DNA replication checkpoint.
authors.affiliation: Jacques Monod Institute, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Batool
authors.initials: B
authors.lastname: Ossareh-Nazari
authors.affiliation: Jacques Monod Institute, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Anthi
authors.initials: A
authors.lastname: Katsiarimpa
authors.affiliation: Jacques Monod Institute, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Merlet
authors.affiliation: Jacques Monod Institute, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France lionel.pintard@ijm.fr.
authors.forename: Lionel
authors.identifier: 0000-0003-0286-4630
authors.initials: L
authors.lastname: Pintard
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D005820:Genetic Testing; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D021122:Protein Subunits; D034622:RNA Interference; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D018121:Receptors, Cytokine; D044767:Ubiquitin-Protein Ligases
keywords: C. elegans; Cullin-RING E3-Ligases; DNA replication; Mutant Screen Report