Regulation of XPG-DNA damage binding dynamics by pre- and post-incision nucleotide excision repair factors and EXO1

Muniesa-Vargas, A.; Ribeiro-Silva, C.; Geverts, B.; Davo-Martinez, C.; van de Grint, J.; Ganpat, M.; Thijssen, K. L.; Pothof, J.; Houtsmuller, A.; Theil, A. F.; Vermeulen, W.; Lans, H.

doi:10.1101/2024.12.06.627128

bioRxiv · 10.1101/2024.12.06.627128

Regulation of XPG-DNA damage binding dynamics by pre- and post-incision nucleotide excision repair factors and EXO1

Muniesa-Vargas, A.·Ribeiro-Silva, C.·Geverts, B.·Davo-Martinez, C.·van de Grint, J.·Ganpat, M.·Thijssen, K. L.·Pothof, J.·Houtsmuller, A.·Theil, A. F.·Vermeulen, W.·Lans, H.

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Abstract

The XPG endonuclease plays a crucial role in nucleotide excision repair (NER) and other genome maintenance pathways. Precise regulation of XPG recruitment and activity during DNA repair is essential to avoid erroneous DNA incisions and genomic instability. In this study, we employed live-cell imaging to investigate how XPG function is regulated during NER, focusing on its dynamic interactions with key factors involved in the pre- and post-incision steps. We found that TFIIH and XPA facilitate the recruitment and association of XPG with DNA damage, and that XPG localizes separately from TFIIH to UV-induced lesions. Furthermore, our results show that XPGs dissociation from DNA damage is triggered by its own incision activity as well as by that of XPF. Additionally, the exonuclease EXO1 promotes XPG dissociation, likely by processing incised DNA, even in the absence of XPG-mediated incision. Our findings help to better understand the regulatory mechanisms that control XPG activity during NER and provide important insights into the complex dynamics of the repair process.

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Muniesa-Vargas, A., Ribeiro-Silva, C., Geverts, B., Davo-Martinez, C., van de Grint, J., Ganpat, M., Thijssen, K. L., Pothof, J., Houtsmuller, A., Theil, A. F., Vermeulen, W., Lans, H.. 2024-12-09. Regulation of XPG-DNA damage binding dynamics by pre- and post-incision nucleotide excision repair factors and EXO1. https://doi.org/10.1101/2024.12.06.627128

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