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

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

Autor 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
Instituição Univ Manitoba
Universidade Federal de São Paulo (UNIFESP)
Univ Parma
Resumo 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.
Assunto centromere
nuclear organization
Robertsonian chromosome
genomic instability
Idioma Inglês
Data 2007-07-01
Publicado em Neoplasia. Ann Arbor: Neoplasia Press, v. 9, n. 7, p. 578-U1, 2007.
ISSN 1522-8002 (Sherpa/Romeo, fator de impacto)
Editor Neoplasia Press
Extensão 578-U1
Fonte http://dx.doi.org/10.1593/neo.07355
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000248495100007
URI http://repositorio.unifesp.br/handle/11600/29836

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