c-Myc-dependent formation of robertsonian translocation chromosomes in mouse cells

被引:26
作者
Guffei, Amanda
Lichtensztejn, Zelda
Silva, Amanda Goncalves dos Santos
Louis, Sherif F.
Caporali, Andrea
Mai, Sabine
机构
[1] Univ Manitoba, Manitoba Inst Cell Biol, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
[2] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Disciplina Imunol, BR-04023062 Sao Paulo, Brazil
[3] Univ Parma, Dipartimento Med Sperimentale, Sez Biochim Biochim Clin & Biochim Esercizo Fis, I-43100 Parma, Italy
来源
NEOPLASIA | 2007年 / 9卷 / 07期
关键词
centromere; nuclear organization; Robertsonian chromosome; c-Myc; genomic instability;
D O I
10.1593/neo.07355
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Robertsonian (Rb) translocation chromosomes occur in human and murine cancers and involve the aberrant joining of two acrocentric chromosomes in humans and two telocentric chromosomes in mice. Mechanisms leading to their generation remain elusive, but models for their formation have been proposed. They include breakage of centromeric sequences and their subsequent fusions, centric misdivision, misparing between highly repetitive sequences of p- tel or p- arm repeats, and recombinational joining of centromeres and/ or centromeric fusions. Here, we have investigated the role of the oncoprotein c- Myc in the formation of Rb chromosomes in mouse cells harboring exclusively telocentric chromosomes. In mouse plasmacytoma cells with constitutive c- Myc deregulation and in immortalized mouse lymphocytes with conditional c-Myc expression, we show that positional remodeling of centromeres in interphase nuclei coincides with the formation of Rb chromosomes. Furthermore, we demonstrate that c-Myc deregulation in a myc box II - dependent manner is sufficient to induce Rb translocation chromosomes. Because telomeric signals are present at all joined centromeres of Rb chromosomes, we conclude that c-Myc mediates Rb chromosome formation in mouse cells by telomere fusions at centromeric termini of telocentric chromosomes. Our findings are relevant to the understanding of nuclear chromosome remodeling during the initiation of genomic instability and tumorigenesis.
引用
收藏
页码:578 / U1
页数:12
相关论文
共 55 条
  • [1] Conditional transgenic models define how MYC initiates and maintains tumorigenesis
    Arvanitis, Constadina
    Felsher, Dean W.
    [J]. SEMINARS IN CANCER BIOLOGY, 2006, 16 (04) : 313 - 317
  • [2] Spectral karyotyping identifies recurrent complex rearrangements of chromosomes 8, 17, and 20 in osteosarcomas
    Bayani, J
    Zielenska, M
    Pandita, A
    Al-Romaih, K
    Karaskova, J
    Harrison, K
    Bridge, JA
    Sorensen, P
    Thorner, P
    Squire, JA
    [J]. GENES CHROMOSOMES & CANCER, 2003, 36 (01) : 7 - 16
  • [3] Chromosomes and speciation in Mus musculus domesticus
    Capanna, E
    Castiglia, R
    [J]. CYTOGENETIC AND GENOME RESEARCH, 2004, 105 (2-4) : 375 - 384
  • [4] Telomeric aggregates and end-to-end chromosomal fusions require myc box II
    Caporali, A.
    Wark, L.
    Vermolen, B. J.
    Garini, Y.
    Mai, S.
    [J]. ONCOGENE, 2007, 26 (10) : 1398 - 1406
  • [5] The three-dimensional organization of telomeres in the nucleus of mammalian cells
    Chuang, Tony Chih Yuan
    Moshir, Sharareh
    Garini, Yuval
    Chuang, Alice Ya-Chun
    Young, Ian T.
    Vermolen, Bart
    van den Doel, Richard
    Mougey, Virginie
    Perrin, Mathilde
    Braun, Martina
    Kerr, Paul Donald
    Fest, Thierry
    Boukamp, Petra
    Mai, Sabine
    [J]. BMC BIOLOGY, 2004, 2 (1)
  • [6] Transient excess of MYC activity can elicit genomic instability and tumorigenesis
    Felsher, DW
    Bishop, JM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) : 3940 - 3944
  • [7] Uncoupling of genomic instability and tumorigenesis in a mouse model of Burkitt's lymphoma expressing a conditional box II-deleted Myc protein
    Fest, T
    Guffei, A
    Williams, G
    Silva, S
    Mai, S
    [J]. ONCOGENE, 2005, 24 (18) : 2944 - 2953
  • [8] c-MYC overexpression in Ba/F3 cells simultaneously elicits genomic instability and apoptosis
    Fest, T
    Mougey, V
    Dalstein, V
    Hagerty, M
    Milette, D
    Silva, S
    Mai, S
    [J]. ONCOGENE, 2002, 21 (19) : 2981 - 2990
  • [9] MYC recruits the TIP60 histone acetyltransferase complex to chromatin
    Frank, SR
    Parisi, T
    Taubert, S
    Fernandez, P
    Fuchs, M
    Chan, HM
    Livingston, DM
    Amati, B
    [J]. EMBO REPORTS, 2003, 4 (06) : 575 - 580
  • [10] Robertsonian translocations in wheat arise by centric misdivision of univalents at anaphase I and rejoining of broken centromeres during interkinesis of meiosis II
    Friebe, B
    Zhang, P
    Linc, G
    Gill, BS
    [J]. CYTOGENETIC AND GENOME RESEARCH, 2005, 109 (1-3) : 293 - 297