Universität zu Köln

Edifizi, Diletta, Nolte, Hendrik, Babu, Vipin ORCID: 0000-0002-0001-8783, Castells-Roca, Laia ORCID: 0000-0002-4604-9999, Mueller, Michael M., Brodesser, Susanne, Krueger, Marcus ORCID: 0000-0003-2008-4582 and Schumacher, Bjoern (2017). Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans. Cell Reports, 20 (9). S. 2026 - 2044. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage. We derive metabolic changes indicative of a tissue maintenance program and implicate an autophagy-mediated proteostatic response. We assign central roles for the insulin-, EGF-, and AMPK-like signaling pathways in orchestrating the adaptive response to DNA damage. Our results provide insights into the DNA damage responses in the organismal context.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Edifizi, Diletta UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Babu, Vipin UNSPECIFIED orcid.org/0000-0002-0001-8783 UNSPECIFIED Castells-Roca, Laia UNSPECIFIED orcid.org/0000-0002-4604-9999 UNSPECIFIED Mueller, Michael M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221394
DOI:	10.1016/j.celrep.2017.08.028
Journal or Publication Title:	Cell Reports
Volume:	20
Number:	9
Page Range:	S. 2026 - 2044
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; LIFE-SPAN; PROTEOMICS ANALYSIS; GENOME INSTABILITY; NUCLEAR-ENVELOPE; RIC-8 SYNEMBRYN; PROTEIN; PATHWAY; GROWTH; REVEALS Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22139