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

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 o...

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Bibliographic Details
Main Authors: Mariangela Sabatella, Karen L. Thijssen, Carlota Davó-Martínez, Wim Vermeulen, Hannes Lans
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Cell Reports
Subjects:
XPC
CSB
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720315977
Description
Summary: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.
ISSN:2211-1247