RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2 LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans - C.elegans Hérédité et Développement Access content directly
Journal Articles G3 Year : 2016

RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2 LRR-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 CRL2 LRR-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 CRL2 LRR-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.
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hal-01404139 , version 1 (28-11-2016)

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Batool Ossareh-Nazari, Anthi Katsiarimpa, Jorge Merlet, Lionel Pintard. RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2 LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans. G3, 2016, 6 (10), pp.3431-3442. ⟨10.1534/g3.116.033043⟩. ⟨hal-01404139⟩
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