The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions

Jill Moser, Marcel Volker, Hanneke Kool, Sergei Alekseev, Harry Vrieling, Akira Yasui, Albert A. Van Zeeland, Leon H.F. Mullenders

    Research output: Contribution to journalArticlepeer-review

    131 Citations (Scopus)

    Abstract

    Previous studies point to the XPC-hHR23B complex as the principal initiator of global genome nucleotide excision repair (NER) pathway, responsible for the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) in human cells. However, the UV-damaged DNA binding protein (UV-DDB) has also been proposed as a damage recognition factor involved in repair of UV-photoproducts, especially CPD. Here, we show in human XP-E cells (UV-DDB deficient) that the incision complex formation at UV-induced lesions was severely diminished in locally damaged nuclear spots. Repair kinetics of CPD and 6-4PP in locally and globally UV-irradiated normal human and XP-E cells demonstrate that UV-DDB can mediate efficient targeting of XPC-hHR23B and other NER factors to 6-4PP. The data is consistent with a mechanism in which UV-DDB forms a stable complex when bound to a 6-4PP, allowing subsequent repair proteins - starting with XPC-hHR23B - to accumulate, and verify the lesion, resulting in efficient 6-4PP repair. These findings suggest that (i) UV-DDB accelerates repair of 6-4PP, and at later time points also CPD, (ii) the fraction of 6-4PP that can be bound by UV-DDB is limited due to its low cellular quantity and fast UV dependent degradation, and (iii) in the absence of UV-DDB a slow XPC-hHR23B dependent pathway is capable to repair 6-4PP, and to some extent also CPD.

    Original languageEnglish
    Pages (from-to)571-582
    Number of pages12
    JournalDNA Repair
    Volume4
    Issue number5
    DOIs
    Publication statusPublished - 2005 May 2

    Keywords

    • 6-4 Photoproducts
    • Cylcobutane pyrimidine dimmers
    • Nucleotide excision repair
    • UV-damaged DNA binding protein
    • Xeroderma pigmentosum group E

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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