Kinetic gating mechanism of DNA damage recognition by Rad4/XPC [electronic resource].
- Washington, D.C. : United States. Dept. of Energy, 2015. and Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- Article numbers 5,849 : digital, PDF file
- Additional Creators:
- Argonne National Laboratory, United States. Department of Energy, and United States. Department of Energy. Office of Scientific and Technical Information
- Restrictions on Access:
- Free-to-read Unrestricted online access
- The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Lastly, kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.
- Published through SciTech Connect., 01/06/2015., "123614", Nature Communications 6 ISSN 2041-1723 AM, and Xueijing Chen; Yogambigai Velmurugu; Guanqun Zheng; Beomseok Park; Yoonjung Shim; Youngchang Kim; Lili Liu; Bennett Van Houten; Chaun He; Anjum Ansari; Jung -Hyun Min.
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