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

Amanda Guffei, Zelda Lichtensztejn, Amanda Gonçalves Dos Santos Silva, Sherif F Louis, Andrea Caporali, Sabine Mai

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)578-88
Number of pages11
JournalNeoplasia
Volume9
Issue number7
Publication statusPublished - Jul 2007

Keywords

  • Animals
  • Cell Line, Tumor
  • Centromere
  • Chromosomal Instability
  • Chromosomes, Mammalian
  • Mice
  • Plasmacytoma
  • Proto-Oncogene Proteins c-myc
  • Telomere
  • Translocation, Genetic

Fingerprint

Dive into the research topics of 'c-Myc-dependent formation of Robertsonian translocation chromosomes in mouse cells'. Together they form a unique fingerprint.

Cite this