Two-stage dynamic DNA quality check by Xeroderma Pigmentosum group C protein

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2009
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Camenisch, Ulrike
Träutlein, Daniel
Clement, Flurina C.
Fei, Jia
Naegeli, Hanspeter
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Zusammenfassung

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 Biowissenschaften, Biologie
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DNA repair, genome stability, protein dynamics
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ISO 690CAMENISCH, 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. 2009, 28(16), pp. 2387-2399. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1038/emboj.2009.187
BibTex
@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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