Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Young Hyun You, Dong Hyun Lee, Jung Hoon Yoon, Satoshi Nakajima, Akira Yasui, Gerd P. Pfeifer

    Research output: Contribution to journalArticlepeer-review

    198 Citations (Scopus)

    Abstract

    The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 × 10-5 to 34 × 10-5 (background, 8-10 × 10-5). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 × 10 -5 to 28 × 10-5 (background, 6-10 × 10 -5). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.

    Original languageEnglish
    Pages (from-to)44688-44694
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume276
    Issue number48
    DOIs
    Publication statusPublished - 2001 Nov 30

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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