Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans

Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M. Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish
Pages (from-to)2026-2043
Number of pages18
JournalCell Reports
Volume20
Issue number9
DOIs
StatePublished - 29 Aug 2017
Externally publishedYes

Keywords

  • Caenorhabditis elegans
  • DNA damage response
  • DNA repair
  • aging
  • lipidomics
  • nucleotide excision repair
  • proteomics

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