RRC ID 53319
著者 Ossareh-Nazari B, Katsiarimpa A, Merlet J, Pintard L.
タイトル RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans.
ジャーナル G3 (Bethesda)
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-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.
巻・号 6(10)
ページ 3431-3442
公開日 2016-10-13
DOI 10.1534/g3.116.033043
PII g3.116.033043
PMID 27543292
PMC PMC5068962
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism DNA Replication* Epistasis, Genetic* Gene Expression Regulation* Genetic Testing Multiprotein Complexes / metabolism Mutation Protein Subunits RNA Interference* Receptors, Cytokine / genetics* Receptors, Cytokine / metabolism Ubiquitin-Protein Ligases / genetics* Ubiquitin-Protein Ligases / metabolism
IF 2.781
引用数 6
リソース情報
線虫 tm3543