Tissue-Specific DNA Repair Activity of ERCC-1/XPF-1

Cell Rep. 2021 Jan 12;34(2):108608. doi: 10.1016/j.celrep.2020.108608.

Abstract

Hereditary DNA repair defects affect tissues differently, suggesting that in vivo cells respond differently to DNA damage. Knowledge of the DNA damage response, however, is largely based on in vitro and cell culture studies, and it is currently unclear whether DNA repair changes depending on the cell type. Here, we use in vivo imaging of the nucleotide excision repair (NER) endonuclease ERCC-1/XPF-1 in C. elegans to demonstrate tissue-specific NER activity. In oocytes, XPF-1 functions as part of global genome NER (GG-NER) to ensure extremely rapid removal of DNA-helix-distorting lesions throughout the genome. In contrast, in post-mitotic neurons and muscles, XPF-1 participates in NER of transcribed genes only. Strikingly, muscle cells appear more resistant to the effects of DNA damage than neurons. These results suggest a tissue-specific organization of the DNA damage response and may help to better understand pleiotropic and tissue-specific consequences of accumulating DNA damage.

Keywords: C. elegans; CSB; DNA damage response; DNA repair; ERCC1/XPF; XPC; nucleotide excision repair; tissue specificity; transcription; transcription-coupled nucleotide excision repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / metabolism*
  • Female
  • Muscles / metabolism
  • Muscles / radiation effects
  • Neurons / metabolism
  • Neurons / radiation effects
  • Oocytes / metabolism
  • Oocytes / radiation effects
  • Organ Specificity
  • Ultraviolet Rays

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Endonucleases
  • XPF-1 protein, C elegans
  • DNA Helicases