c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus.
Proc Natl Acad Sci U S A
; 102(27): 9613-8, 2005 Jul 05.
Article
em En
| MEDLINE
| ID: mdl-15983382
ABSTRACT
In previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycles of telomeric aggregate formation in interphase nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion cycles that are initiated by end-to-end telomeric fusions of chromosomes. Subsequent to initial chromosomal breakages, new fusions follow and the breakage-bridge-fusion cycles continue. During this time, nonreciprocal translocations are generated. c-Myc-dependent remodeling of the organization of telomeres thus precedes the onset of genomic instability and subsequently leads to chromosomal rearrangements. Our findings reveal that c-Myc possesses the ability to structurally modify chromosomes through telomeric fusions, thereby reorganizing the genetic information.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico
/
Regulação Neoplásica da Expressão Gênica
/
Proteínas Proto-Oncogênicas c-myc
/
Telômero
/
Cromossomos de Mamíferos
/
Instabilidade Cromossômica
/
Interfase
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2005
Tipo de documento:
Article