Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells

Yuko Yamaguchi-Iwai, Eiichiro Sonoda, Masao S. Sasaki, Ciaran Morrison, Tokuko Haraguchi, Yasushi Hiraoka, Yukiko M. Yamashita, Takashi Yagi, Minoru Takata, Carolyn Price, Naoki Kakazu, Shunichi Takeda

    Research output: Contribution to journalArticle

    226 Scopus citations

    Abstract

    Yeast Mre11 functions with Rad50 and Xrs2 in a complex that has pivotal roles in homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand break (DSB) repair pathways. Vertebrate Mre11 is essential. Conditionally, MRE11 null chicken DT40 cells accumulate chromosome breaks and die upon Mre11 repression, showing frequent centrosome amplification. Mre11 deficiency also causes increased radiosensitivity and strongly reduced targeted integration frequencies. Mre11 is, therefore, crucial for HR and essential in mitosis through its role in chromosome maintenance by recombinational repair. Surprisingly perhaps, given the role of Mre11 in yeast NHEJ, disruption of NHEJ by deletion of KU70 greatly exacerbates the effects of MRE11 deficiency, revealing a significant Mre11-independent component of metazoan NHEJ.

    Original languageEnglish (US)
    Pages (from-to)6619-6629
    Number of pages11
    JournalEMBO Journal
    Volume18
    Issue number23
    StatePublished - Dec 1 1999

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    Keywords

    • Chromosomal aberration
    • Double-strand break repair
    • DT40
    • Homologous recombination
    • Mre11

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

    Cite this

    Yamaguchi-Iwai, Y., Sonoda, E., Sasaki, M. S., Morrison, C., Haraguchi, T., Hiraoka, Y., Yamashita, Y. M., Yagi, T., Takata, M., Price, C., Kakazu, N., & Takeda, S. (1999). Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells. EMBO Journal, 18(23), 6619-6629.