RRC ID 55862
著者 Bianco JN, Schumacher B.
タイトル MPK-1/ERK pathway regulates DNA damage response during development through DAF-16/FOXO.
ジャーナル Nucleic Acids Res
Abstract Ultraviolet (UV) induces distorting lesions to the DNA that can lead to stalling of the RNA polymerase II (RNAP II) and that are removed by transcription-coupled nucleotide excision repair (TC-NER). In humans, mutations in the TC-NER genes CSA and CSB lead to severe postnatal developmental defects in Cockayne syndrome patients. In Caenorhabditis elegans, mutations in the TC-NER genes csa-1 and csb-1, lead to developmental growth arrest upon UV treatment. We conducted a genetic suppressor screen in the nematode to identify mutations that could suppress the developmental defects in csb-1 mutants. We found that mutations in the ERK1/2 MAP kinase mpk-1 alleviate the developmental retardation in TC-NER mutants, while constitutive activation of the RAS-MAPK pathway exacerbates the DNA damage-induced growth arrest. We show that MPK-1 act via insulin/insulin-like signaling pathway and regulates the FOXO transcription factor DAF-16 to mediate the developmental DNA damage response.
巻・号 46(12)
ページ 6129-6139
公開日 2018-7-6
DOI 10.1093/nar/gky404
PII 5000020
PMID 29788264
PMC PMC6159517
MeSH Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* DNA Repair* Forkhead Transcription Factors / metabolism* Larva / enzymology Larva / genetics Larva / metabolism MAP Kinase Signaling System* Mitogen-Activated Protein Kinase 1 / genetics* Mitogen-Activated Protein Kinase 1 / metabolism Mutation Suppression, Genetic
IF 11.147
引用数 1
リソース情報
線虫 tm4539