Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein.
Proc Natl Acad Sci U S A
; 108(35): 14491-6, 2011 Aug 30.
Article
en En
| MEDLINE
| ID: mdl-21849621
ABSTRACT
Stability and repair of DNA is of principal importance in cell survival. Heme oxygenase-1 (HO-1; Hmox1) is critical in maintaining cellular homeostasis, in large part through its ability to generate CO, but neither molecule has been studied in the setting of DNA damage. Naïve Hmox1(-/-) mice exhibit excessive tissue levels of γ-histone H2A, whereas administration of genotoxic stressors or irradiation in HO-1-deficient cells resulted in loss of ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein and breast cancer 1, early onset induction with dysfunctional γ-H2AX foci and marked elevations in DNA damage. HO-1 induction or exposure to CO induced homologous recombination-mediated DNA repair through ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein. In vivo, exposure of mice to CO followed by genotoxin (Adriamycin) or radiation-induced injury led to diminished tissue DNA damage and improved survival. We characterize a joint role for HO-1 and the gasotransmitter CO for appropriate DNA repair and provide a mechanism for their potent cytoprotective effects in various pathologies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN
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Monóxido de Carbono
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Proteínas Serina-Treonina Quinasas
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Proteínas de Ciclo Celular
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Proteínas Supresoras de Tumor
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Proteínas de Unión al ADN
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Reparación del ADN
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Hemo-Oxigenasa 1
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos