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Publication Detail

Title: Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins.

Authors: Kumar, Namrata; Theil, Arjan F; Roginskaya, Vera; Ali, Yasmin; Calderon, Michael; Watkins, Simon C; Barnes, Ryan P; Opresko, Patricia L; Pines, Alex; Lans, Hannes; Vermeulen, Wim; Van Houten, Bennett

Published In Nat Commun, (2022 02 21)

Abstract: UV-DDB, consisting of subunits DDB1 and DDB2, recognizes UV-induced photoproducts during global genome nucleotide excision repair (GG-NER). We recently demonstrated a noncanonical role of UV-DDB in stimulating base excision repair (BER) which raised several questions about the timing of UV-DDB arrival at 8-oxoguanine (8-oxoG), and the dependency of UV-DDB on the recruitment of downstream BER and NER proteins. Using two different approaches to introduce 8-oxoG in cells, we show that DDB2 is recruited to 8-oxoG immediately after damage and colocalizes with 8-oxoG glycosylase (OGG1) at sites of repair. 8-oxoG removal and OGG1 recruitment is significantly reduced in the absence of DDB2. NER proteins, XPA and XPC, also accumulate at 8-oxoG. While XPC recruitment is dependent on DDB2, XPA recruitment is DDB2-independent and transcription-coupled. Finally, DDB2 accumulation at 8-oxoG induces local chromatin unfolding. We propose that DDB2-mediated chromatin decompaction facilitates the recruitment of downstream BER proteins to 8-oxoG lesions.

PubMed ID: 35190564 Exiting the NIEHS site

MeSH Terms: Cell Line, Tumor; Chromatin Assembly and Disassembly; Chromatin/metabolism; DNA Damage/radiation effects; DNA Glycosylases/metabolism; DNA Repair*; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism*; Gene Knockdown Techniques; Gene Knockout Techniques; Guanine/analogs & derivatives*; Guanine/metabolism; Guanine/radiation effects; HEK293 Cells; Humans; Ultraviolet Rays/adverse effects; Xeroderma Pigmentosum Group A Protein/genetics; Xeroderma Pigmentosum Group A Protein/metabolism

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