In Vivo Recruitment of XPC to UV-induced Cyclobutane Pyrimidine Dimers by the DDB2 Gene Product

Maureen E. Fitch, Satoshi Nakajima, Akira Yasui, James M. Ford

    Research output: Contribution to journalArticlepeer-review

    176 Citations (Scopus)

    Abstract

    The initial step in mammalian nucleotide excision repair (NER) of the major UV-induced photoproducts, cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs), requires lesion recognition. It is believed that the heterodimeric proteins XPC/hHR23B and UV-DDB (UV-damaged DNA binding factor, composed of the p48 and p127 subunits) perform this function in genomic DNA, but their requirement and lesion specificity in vivo remains unknown. Using repair-deficient xeroderma pigmentosum (XP)-A cells that stably express photoproduct-specific photolyases, we determined the binding characteristics of p48 and XPC to either CPDs or 6-4PPs in vivo. p48 localized to UV-irradiated sites that contained either CPDs or 6-4PPs. However, XPC localized only to UV-irradiated sites that contained 6-4PPs, suggesting that XPC does not efficiently recognize CPDs in vivo. XPC did localize to CPDs when p48 was overexpressed in the same cell, signifying that p48 activates the recruitment of XPC to CPDs and may be the initial recognition factor in the NER pathway.

    Original languageEnglish
    Pages (from-to)46906-46910
    Number of pages5
    JournalJournal of Biological Chemistry
    Volume278
    Issue number47
    DOIs
    Publication statusPublished - 2003 Nov 21

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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