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

被引:230
作者
Yamaguchi-Iwai, Y
Sonoda, E
Sasaki, MS
Morrison, C
Haraguchi, T
Hiraoka, Y
Yamashita, YM
Yagi, T
Takata, M
Price, C
Kakazu, N
Takeda, S
机构
[1] Kyoto Univ, Bayer Chair Dept Mol Immunol & Allergol, Fac Med, Sakyo Ku, Kyoto 6068501, Japan
[2] Kyoto Univ, Ctr Radiat Biol, Sakyo Ku, Kyoto 6068501, Japan
[3] Kansai Adv Res Ctr, Commun Res Lab, Kobe, Hyogo 6512401, Japan
[4] Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA
[5] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA
[6] Kyoto Prefectural Univ Med, Kyoto 6020841, Japan
关键词
chromosomal aberration; double-strand break repair; DT40; homologous recombination; Mre11;
D O I
10.1093/emboj/18.23.6619
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6619 / 6629
页数:11
相关论文
共 65 条
  • [1] AGARD DA, 1989, METHOD CELL BIOL, V30, P353
  • [2] AJIMURA M, 1993, GENETICS, V133, P51
  • [3] Reduced X-ray resistance and homologous recombination frequencies in a RAD54(-/-) mutant of the chicken DT40 cell line
    Bezzubova, O
    Silbergleit, A
    YamaguchiIwai, Y
    Takeda, S
    Buerstedde, JM
    [J]. CELL, 1997, 89 (02) : 185 - 193
  • [4] Xrcc3 is required for assembly of Rad51 complexes in vivo
    Bishop, DK
    Ear, U
    Bhattacharyya, A
    Calderone, C
    Beckett, M
    Weichselbaum, RR
    Shinohara, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (34) : 21482 - 21488
  • [5] Identification of a Saccharomyces cerevisiae Ku80 homologue: Roles in DNA double strand break rejoining and in telomeric maintenance
    Boulton, SJ
    Jackson, SP
    [J]. NUCLEIC ACIDS RESEARCH, 1996, 24 (23) : 4639 - 4648
  • [6] Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways
    Boulton, SJ
    Jackson, SP
    [J]. EMBO JOURNAL, 1996, 15 (18) : 5093 - 5103
  • [7] Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing
    Boulton, SJ
    Jackson, SP
    [J]. EMBO JOURNAL, 1998, 17 (06) : 1819 - 1828
  • [8] INCREASED RATIO OF TARGETED TO RANDOM INTEGRATION AFTER TRANSFECTION OF CHICKEN B-CELL LINES
    BUERSTEDDE, JM
    TAKEDA, S
    [J]. CELL, 1991, 67 (01) : 179 - 188
  • [9] Requirement for p53 and p21 to sustain G2 arrest after DNA damage
    Bunz, F
    Dutriaux, A
    Lengauer, C
    Waldman, T
    Zhou, S
    Brown, JP
    Sedivy, JM
    Kinzler, KW
    Vogelstein, B
    [J]. SCIENCE, 1998, 282 (5393) : 1497 - 1501
  • [10] The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: Linkage of double-strand break repair to the cellular DNA damage response
    Carney, JP
    Maser, RS
    Olivares, H
    Davis, EM
    Le Beau, M
    Yates, JR
    Hays, L
    Morgan, WF
    Petrini, JHJ
    [J]. CELL, 1998, 93 (03) : 477 - 486