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MPK-1/ERK pathway regulates DNA damage response during development through DAF-16/FOXO.

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.

SUBMITTER: Bianco JN

PROVIDER: S-EPMC6159517 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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MPK-1/ERK pathway regulates DNA damage response during development through DAF-16/FOXO.

Bianco Julien N JN Schumacher Björn B

Nucleic acids research 20180701 12

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 ...[more]

PMID: 29788264

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DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage [N2, daf-2, daf-16, daf-2;daf-16]

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2015-08-27 | GSE72426 | GEO

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