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 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:
CreatorsEmailORCIDORCID Put Code
Edifizi, DilettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Babu, VipinUNSPECIFIEDorcid.org/0000-0002-0001-8783UNSPECIFIED
Castells-Roca, LaiaUNSPECIFIEDorcid.org/0000-0002-4604-9999UNSPECIFIED
Mueller, Michael M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CAENORHABDITIS-ELEGANS; LIFE-SPAN; PROTEOMICS ANALYSIS; GENOME INSTABILITY; NUCLEAR-ENVELOPE; RIC-8 SYNEMBRYN; PROTEIN; PATHWAY; GROWTH; REVEALSMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22139

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