Universität zu Köln

Bianco, Julien N. and Schumacher, Bjoern (2018). MPK-1/ERK pathway regulates DNA damage response during development through DAF-16/FOXO. Nucleic Acids Res., 46 (12). S. 6129 - 6140. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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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 ele-gans, 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bianco, Julien N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-179887
DOI:	10.1093/nar/gky404
Journal or Publication Title:	Nucleic Acids Res.
Volume:	46
Number:	12
Page Range:	S. 6129 - 6140
Date:	2018
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1362-4962
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; EPIDERMAL-GROWTH-FACTOR; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAYS; COCKAYNE-SYNDROME; UV-IRRADIATION; C-ELEGANS; ERK; ACTIVATION; KINASE Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17988