RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery inCaenorhabditis elegans | Zendy

Batool OssarehNazari | Zendy; Anthi Katsiarimpa | Zendy; Jorge Merlet | Zendy; Lionel Pintard | Zendy

Open Access

RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery inCaenorhabditis elegans

Author(s) -

Batool OssarehNazari,

Anthi Katsiarimpa,

Jorge Merlet,

Lionel Pintard

Publication year - 2016

Publication title -

g3 genes genomes genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.468

H-Index - 66

ISSN - 2160-1836

DOI - 10.1534/g3.116.033043

Subject(s) - biology , replisome , ubiquitin ligase , helicase , cullin , dna replication , genetics , ubiquitin protein ligases , dna replication factor cdt1 , microbiology and biotechnology , caenorhabditis elegans , control of chromosome duplication , pre replication complex , rna interference , origin recognition complex , replication factor c , ubiquitin , eukaryotic dna replication , dna , gene , rna

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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