Tissue-Specific DNA Repair Activity of ERCC-1/XPF-1
Mariangela Sabatella,
Karen L. Thijssen,
Carlota Davó-Martínez,
Wim Vermeulen,
Hannes Lans
Affiliations
Mariangela Sabatella
Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
Karen L. Thijssen
Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
Carlota Davó-Martínez
Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
Wim Vermeulen
Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Corresponding author
Hannes Lans
Department of Molecular Genetics, Oncode Institute, Erasmus MC, University Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Corresponding author
Summary: 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.
