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| Título: | Inhibitor of growth 1 (ING1) acts at early steps of multiple DNA repair pathways |
Autor: | Menéndez, Camino CSIC; Palmero, Ignacio CSIC ORCID | Palabras clave: | ING1 DNA repair p53 Chromatin structure |
Fecha de publicación: | jun-2013 | Editor: | Springer Nature | Citación: | Molecular and Cellular Biochemistry 378(1-2): 117-126 (2013) | Resumen: | ING proteins are tumor suppressors involved in the regulation of gene transcription, cell cycle arrest, apoptosis, and senescence. Here, we show that ING1b expression is upregulated by several DNA-damaging agents, in a p53-independent manner. ING1b stimulates DNA repair of a variety of DNA lesions requiring activation of multiple DNA repair pathways. Moreover, Ing1 −/− cells showed impaired genomic DNA repair after H2O2 and neocarzinostatin treatment and this defect was reverted by overexpression of ING1b. Two tumor-derived ING1 mutants failed to promote DNA repair highlighting the physiological importance of the integrity of the PHD domain for ING1b DNA repair activity and suggesting a role in the prevention of tumor progression. Ing−/− cells showed higher basal levels of γ-H2AX and, upon DNA damage, γ-H2AX increase was greater and with faster kinetics compared to wild-type cells. Chromatin relaxation by Trichostatin A led to an exacerbated damage signal in both types of cells, but this effect was dependent on Ing1 status, and more pronounced in wild-type cells. Our results suggest that ING1 acts at early stages of the DNA damage response activating a variety of repair mechanisms and that this function of ING1 is targeted in tumors. | Descripción: | et al. | Versión del editor: | http://dx.doi.org/10.1007/s11010-013-1601-2 | URI: | http://hdl.handle.net/10261/78244 | DOI: | 10.1007/s11010-013-1601-2 | ISSN: | 0300-8177 | E-ISSN: | 1573-4919 |
| Aparece en las colecciones: | (IIBM) Artículos |
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| accesoRestringido.pdf | 15,38 kB | Adobe PDF |  Visualizar/Abrir |
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