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Título :	Differential expression of TP53 associated genes in Fanconi anemia cells after mitomycin C andhydroxyurea treatment
Creador:	Martinez A
Nivel de acceso:	Open access
Palabras clave :	Reactivos de Enlaces Cruzados - farmacología Anemia de Fanconi - metabolismo Regulación de la Expresión Génica - efectos de drogas Genes p53 - genetica Hidroxiurea - farmacología Mitomicina - farmacología Inhibidores de la Síntesis de Ácidos Nucleicos - farmacología Cross-Linking Reagents - pharmacology Fanconi Anemia - metabolism Gene Expression Regulation - drug effects Genes, p53 - genetics Hydroxyurea - pharmacology Mitomycin - pharmacology Nucleic Acid Synthesis Inhibitors - pharmacology Anemia de Fanconi Hydroxyurea Mitomicina CC TP53 Expresión génica Detención del ciclo celular Apoptosis Fanconi anemia Hydroxyurea Mitomycin C TP53 Gene expression Cell cycle arrest Apoptosis
Descripción :	Fanconi anemia (FA) is a rare, heritable chromosomal instability disease characterized by several congenital defects and cancer predisposition. Functional interactions between specific FA proteins and DNA damage response and repair activities have been reported, but the interplay between these mechanisms for maintaining genomic stability are not well understood. Many DNA damage response proteins are transcriptionally regulated by the tumor suppressor protein p53 (TP53), suggesting an important regulatory role for the DNA damage and stress response pathway. To better understand the association between FA and the DNA damage stress response we analyzed the levels of chromosomal damage and damage mediated gene transcription responses in lymphoblastoid cells derived from normal individuals and patients carrying the most common FA complementation group (FA-A). Chromosomal aberrations were first measured after exposure to mitomicyn C (MMC) or hydroxyurea (HU). Aliquots of the same cell were than assayed for the transcriptional response of 21 DNA damage and stress response genes using quantitative real-time PCR. The FA-A lymphoblastoid cells showed significant increases in the frequency of chromosome aberrations relative to non-FA-A lymphoblastoid lines after MMC treatment. The MMC induced damage was correlated with a general increase in expression of TP53-modulated DNA damage stress response genes involved in processes such as DNA repair, cell cycle progression, and apoptosis. Following HU treatment FA cells showed a decreased induction of CAs with much less transcriptional differences between targeted genes. Overall, the differences between the normal and FA-A cells after genotoxic treatments imply an increased activation and reliance of FA cells on the down-stream activities of TP53 for prevention of cell killing and chromosome damage from interstrand crosslinks but not for general replication arrest and double strand breaks. Furthermore, these results imply a regulatory connection between the FA pathway and activation of TP53 for responding to DNA damage. Alterations in the regulation of the DNA damage response may be related to the complex phenotypes seen in FA patients.
Colaborador(es) u otros Autores:	Hinz JM  Gómez L  Molina B  Acuña H  Jones IM  Frias S  Coleman MA
Fecha de publicación :	2008
Tipo de publicación:	Artículo
Formato:	pdf
Identificador del Recurso :	10.1016/j.mrgentox.2008.06.012
Fuente:	Mutat Res. 656(( 1 - 2 )):1-7
URI :	http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2294
Idioma:	eng
Aparece en las colecciones:	Artículos

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