2. Academic Validation
  3. H3K4me2 regulates the recovery of protein biosynthesis and homeostasis following DNA damage

H3K4me2 regulates the recovery of protein biosynthesis and homeostasis following DNA damage

  • Nat Struct Mol Biol. 2020 Dec;27(12):1165-1177. doi: 10.1038/s41594-020-00513-1.
Siyao Wang 1 2,  David H Meyer 1 2,  Björn Schumacher 3 4 5
Affiliations

Affiliations

  • 1 Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Cologne, Germany.
  • 2 Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • 3 Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Cologne, Germany. bjoern.schumacher@uni-koeln.de.
  • 4 Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. bjoern.schumacher@uni-koeln.de.
  • 5 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. bjoern.schumacher@uni-koeln.de.
PMID: 33046905 DOI: 10.1038/s41594-020-00513-1
Abstract

DNA damage causes Cancer, impairs development and accelerates aging. Transcription-blocking lesions and transcription-coupled repair defects lead to developmental failure and premature aging in humans. Following DNA repair, homeostatic processes need to be reestablished to ensure development and maintain tissue functionality. Here, we report that, in Caenorhabditis elegans, removal of the WRAD complex of the MLL/COMPASS H3K4 methyltransferase exacerbates developmental growth retardation and accelerates aging, while depletion of the H3K4 demethylases SPR-5 and AMX-1 promotes developmental growth and extends lifespan amid ultraviolet-induced damage. We demonstrate that DNA-damage-induced H3K4me2 is associated with the activation of genes regulating RNA transport, splicing, ribosome biogenesis and protein homeostasis and regulates the recovery of protein biosynthesis that ensures survival following genotoxic stress. Our study uncovers a role for H3K4me2 in coordinating the recovery of protein biosynthesis and homeostasis required for developmental growth and longevity after DNA damage.

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