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Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation.
Abdel-Halim, H I; Natarajan, A T; Mullenders, L H F; Boei, J J W A.
Afiliación
  • Abdel-Halim HI; Department of Toxicogenetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands.
J Cell Sci ; 118(Pt 8): 1757-67, 2005 Apr 15.
Article en En | MEDLINE | ID: mdl-15797924
Chromatid interchanges induced by the DNA cross-linking agent mitomycin C (MMC) are over-represented in human chromosomes containing large heterochromatic regions. We found that nearly all exchange breakpoints of chromosome 9 are located within the paracentromeric heterochromatin and over 70% of exchanges involving chromosome 9 are between its homologues. We provide evidence that the required pairing of chromosome 9 heterochromatic regions occurs in G(0)/G(1) and S-phase cells as a result of an active cellular process initiated upon MMC treatment. By contrast, no pairing was observed for a euchromatic paracentromeric region of the equal-sized chromosome 8. The MMC-induced pairing of chromosome 9 heterochromatin is observed in a subset of cells; its percentage closely mimics the frequency of homologous interchanges found at metaphase. Moreover, the absence of pairing in cells derived from XPF patients correlates with an altered spectrum of MMC-induced exchanges. Together, the data suggest that the heterochromatin-specific pairing following MMC treatment reflects the initiation of DNA cross-link repair and the formation of exchanges.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intercambio de Cromátides Hermanas / Daño del ADN / Heterocromatina / Mitomicina / Emparejamiento Cromosómico / Reparación del ADN Límite: Humans Idioma: En Revista: J Cell Sci Año: 2005 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Intercambio de Cromátides Hermanas / Daño del ADN / Heterocromatina / Mitomicina / Emparejamiento Cromosómico / Reparación del ADN Límite: Humans Idioma: En Revista: J Cell Sci Año: 2005 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido