Recruitment of mismatch repair proteins to the site of DNA damage in human cells

Zehui Hong, Jie Jiang, Kazunari Hashiguchi, Mikiko Hoshi, Li Lan, Akira Yasui

    Research output: Contribution to journalArticlepeer-review

    60 Citations (Scopus)

    Abstract

    Mismatch repair (MDM) proteins contribute to genome stability by excising DNA mismatches introduced by DNA polymerase. Although MMR proteins are also known to influence cellular responses to DNA damage, how MMR proteins respond to DNA damage within the cell remains unknown. Here, we show that MMR proteins are recruited immediately to the sites of various types of DNA damage in human cells. MMR proteins are recruited to single-strand breaks in a poly(ADP-ribose)-dependent manner as well as to double-strand breaks. Using mutant cells, RNA interference and expression of fluorescence-tagged proteins, we show that accumulation of MutSβ at the DNA damage site is solely dependent on the PCNA-binding domain of MSH3, and that of MutSα depends on a region near the PCNA-binding domain of MSH6. MSH2 is recruited to the DNA damage site through interactions with either MSH3 or MSH6, and is required for recruitment of MLH1 to the damage site. We found, furthermore, that MutSβ is also recruited to UV-irradiated sites in nucleotide-excision-repair- and PCNA-dependent manners. Thus, MMR and its proteins function not only in replication but also in DNA repair.

    Original languageEnglish
    Pages (from-to)3146-3154
    Number of pages9
    JournalJournal of cell science
    Volume121
    Issue number19
    DOIs
    Publication statusPublished - 2008 Oct 1

    Keywords

    • DNA strand breaks
    • In situ analysis
    • Mismatch repair
    • PCNA
    • UV damage

    ASJC Scopus subject areas

    • Cell Biology

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