Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

Na Young Cheon, Hyun-Suk Kim, Jung-Eun Yeo, Orlando D Schärer, and Ja Yil Lee

Nucleic Acids Res. (2019). doi:10.1093/nar/gkz629

Nucleotide excision repair (NER) is a highly conserved DNA repair pathway in charge of eliminating a diverse repertoire of DNA damages. Xeroderma pigmentosum complementation group C protein (XPC) along with RAD23B and Centrin2, recognizes a variety of NER substrates by sensing the local distortion and/or thermodynamic destabilization of the DNA helix caused by the modified bases. In this study, the authors have visualized the movement of human NER protein XPC-RAD23B on DNA using DNA curtains, a novel single-molecule real-time imaging technique. The study elucidates the motion of the protein complex on damaged and undamaged DNA and provides important insights into how XPC-RAD23B initiates NER. The complex displayed multiple types of motions – with constrained localization of the repair machinery highly correlated with AT-tracks, suggesting that local DNA instability plays a role in the lesion search process.

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