Defective binding of transcriptional repressor ZEB via DNA methylation contributes to increased constitutive levels of p73 in Fanconi anemia cells.

Unidad de Genética Molecular, Hospital Universitario Marques de Valdecilla, Edificio Escuela Universitaria de Enfermeria, Servicio Cantabro de Salud, Av. Valdecilla s/n, 39008 Santander, Spain.
FEBS Letters (Impact Factor: 3.34). 09/2005; 579(21):4610-4. DOI: 10.1016/j.febslet.2005.07.026
Source: PubMed

ABSTRACT Little is known about the molecular mediators of the Fanconi anemia (FA) pathway involved in the machinery that maintains genomic integrity. Here, we report that the levels of p73 and its target genes, are increased in cells derived from FA patients belonging to complementation group A (FA-A). Moreover, functional correction of FA-A cells by gene transfer reduces the expression of p73. We also demonstrate that DNA methylation contributes to increased levels of p73 in FA-A cells by hampering the binding of the transcriptional repressor ZEB to an intronic regulatory region of the p73 gene. Together, our data may help explain the susceptibility of these cells to DNA damaging agents.

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