Two-stage dynamic DNA quality check by Xeroderma Pigmentosum group C protein
Two-stage dynamic DNA quality check by Xeroderma Pigmentosum group C protein
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Date
2009
Authors
Camenisch, Ulrike
Träutlein, Daniel
Clement, Flurina C.
Fei, Jia
Naegeli, Hanspeter
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The EMBO Journal ; 28 (2009), 16. - pp. 2387-2399. - ISSN 0261-4189. - eISSN 1460-2075
Abstract
Xeroderma pigmentosum group C (XPC) protein initiates the DNA excision repair of helix-distorting base lesions. To understand how this versatile subunit searches for aberrant sites within the vast background of normal genomic DNA, the real-time redistribution of fluorescent fusion constructs was monitored after high-resolution DNA damage induction. Bidirectional truncation analyses disclosed a surprisingly short recognition hotspot, comprising approx15% of human XPC, that includes two beta-hairpin domains with a preference for non-hydrogen-bonded bases in double-stranded DNA. However, to detect damaged sites in living cells, these DNA-attractive domains depend on the partially DNA-repulsive action of an adjacent beta-turn extension that promotes the mobility of XPC molecules searching for lesions. The key function of this dynamic interaction surface is shown by a site-directed charge inversion, which results in increased affinity for native DNA, retarded nuclear mobility and diminished repair efficiency. These studies reveal a two-stage discrimination process, whereby XPC protein first deploys a dynamic sensor interface to rapidly interrogate the double helix, thus forming a transient recognition intermediate before the final installation of a more static repair-initiating complex.
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570 Biosciences, Biology
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DNA repair,genome stability,protein dynamics
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CAMENISCH, Ulrike, Daniel TRÄUTLEIN, Flurina C. CLEMENT, Jia FEI, Alfred LEITENSTORFER, Elisa FERRANDO-MAY, Hanspeter NAEGELI, 2009. Two-stage dynamic DNA quality check by Xeroderma Pigmentosum group C protein. In: The EMBO Journal. 28(16), pp. 2387-2399. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1038/emboj.2009.187BibTex
@article{Camenisch2009Twost-979, year={2009}, doi={10.1038/emboj.2009.187}, title={Two-stage dynamic DNA quality check by Xeroderma Pigmentosum group C protein}, number={16}, volume={28}, issn={0261-4189}, journal={The EMBO Journal}, pages={2387--2399}, author={Camenisch, Ulrike and Träutlein, Daniel and Clement, Flurina C. and Fei, Jia and Leitenstorfer, Alfred and Ferrando-May, Elisa and Naegeli, Hanspeter} }
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