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

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

Author Guffei, Amanda Google Scholar
Lichtensztejn, Zelda Google Scholar
Silva, Amanda Goncalves dos Santos Autor UNIFESP Google Scholar
Louis, Sherif F. Google Scholar
Caporali, Andrea Google Scholar
Mai, Sabine Google Scholar
Institution Univ Manitoba
Universidade Federal de São Paulo (UNIFESP)
Univ Parma
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.
Keywords centromere
nuclear organization
Robertsonian chromosome
c-Myc
genomic instability
Language English
Date 2007-07-01
Published in Neoplasia. Ann Arbor: Neoplasia Press, v. 9, n. 7, p. 578-U1, 2007.
ISSN 1522-8002 (Sherpa/Romeo, impact factor)
Publisher Neoplasia Press
Extent 578-U1
Origin http://dx.doi.org/10.1593/neo.07355
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000248495100007
URI http://repositorio.unifesp.br/handle/11600/29836

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