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

Sabatella et al. image the DNA repair endonuclease ERCC-1/XPF-1 in C. elegans to show that nucleotide excision repair exhibits tissue-specific activity. DNA lesions are very rapidly removed from the entire genome in oocytes but only from transcribed genes in somatic cells. Neurons are more sensitive to DNA damage than muscle cells.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.

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