C-Myc Induces Chromosomal Rearrangements Through Telomere and Chromosome Remodeling in the Interphase Nucleus
c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus Sherif F. Louis*†, Bart J. Vermolen†‡, Yuval Garini†‡, Ian T. Young‡, Amanda Guffei*, Zelda Lichtensztejn*, Fabien Kuttler*, Tony C. Y. Chuang*§¶, Sharareh Moshir*ʈ, Virginie Mougey**, Alice Y. C. Chuang*, Paul Donald Kerr§, Thierry Fest**††, Petra Boukampʈ, and Sabine Mai*‡‡ *Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, Canada R3E 0V9; ‡Department of Imaging Science and Technology, Faculty of Applied Sciences, Quantitative Imaging Group, Delft University of Technology, 2628 CJ Delft, The Netherlands; §Department of Otolaryngology Head and Neck Surgery, Health Sciences Centre, GB421-820 Sherbrook Street, Winnipeg, MB, Canada R3A 1R9; ʈDivision of Genetics of Skin Carcinogenesis, German Cancer Research Centre, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; **Hematology Department, IETG Laboratory, University Hospital Jean Minjoz, 25030 Besanc¸on, France; and ††Hematology Department, EA 3889, IFR140 GFAS, University Hospital Pontchaillou, 35033 Rennes, France Edited by George Klein, Karolinska Institutet, Stockholm, Sweden, and approved May 9, 2005 (received for review October 11, 2004) In previous work, we showed that telomeres of normal cells are promotes tumorigenesis (26–30). When c-Myc deregulation is organized within the 3D space of the interphase nucleus in a abolished, in vivo tumorigenesis is reversible, provided that no nonoverlapping and cell cycle-dependent manner. This order is additional mutations had occurred (29–34). distorted in tumor cell nuclei where telomeres are found in close Prompted by the complexity of downstream genetic alterations association forming aggregates of various numbers and sizes. Here that result from c-Myc deregulation, we investigated whether c-Myc we show that c-Myc overexpression induces telomeric aggrega- affected the 3D organization of the mammalian interphase nucleus tions in the interphase nucleus.
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