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 a Journal (Peer & Non Peer)Articlepeer-review

245 Citations (Scopus)

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
Pages (from-to)6619-6629
Number of pages11
JournalEMBO Journal
Volume18
Issue number23
DOIs
Publication statusPublished - 1 Dec 1999
Externally publishedYes

Keywords

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

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