ZNF830 mediates cancer chemoresistance through promoting homologous-recombination repair.
Nucleic Acids Res
; 46(3): 1266-1279, 2018 02 16.
Article
en En
| MEDLINE
| ID: mdl-29244158
ABSTRACT
Homologous recombination (HR), which mediates the repair of DNA double-strand breaks (DSB), is crucial for maintaining genomic integrity and enhancing survival in response to chemotherapy and radiotherapy in human cancers. However, the mechanisms of HR repair in treatment resistance for the improvement of cancer therapy remains unclear. Here, we report that the zinc finger protein 830 (ZNF830) promotes HR repair and the survival of cancer cells in response to DNA damage. Mechanistically, ZNF830 directly participates in DNA end resection via interacting with CtIP and regulating CtIP recruitment to DNA damage sites. Moreover, the recruitment of ZNF830 at DNA damage sites is dependent on its phosphorylation at serine 362 by ATR. ZNF830 directly and preferentially binds to double-strand DNA with its 3' or 5' overhang through the Zinc finger (Znf) domain, facilitating HR repair and maintaining genome stability. Thus, our study identified a novel function of ZNF830 as a HR repair regulator in DNA end resection, conferring the chemoresistance to genotoxic therapy for cancers those that overexpress ZNF830.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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ADN de Neoplasias
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Resistencia a Antineoplásicos
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Factores de Transcripción de Tipo Kruppel
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Reparación del ADN por Recombinación
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2018
Tipo del documento:
Article