Inhibition of the Nedd8 System Sensitizes Cells to DNA Interstrand Cross-linking Agents

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Inhibition of the Nedd8 system sensitizes cells to DNA interstrand cross-linking agents.

The Fanconi anemia pathway is required for repair of DNA interstrand cross-links (ICL). Fanconi anemia pathway-deficient cells are hypersensitive to DNA ICL-inducing drugs such as cisplatin. Conversely, hyperactivation of the Fanconi anemia pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the Fanconi anemia pathw...

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DNA Damage and Cellular Stress Responses Inhibition of the Nedd8 System Sensitizes Cells to DNA Interstrand Cross-linking Agents

The Fanconi anemia pathway is required for repair of DNA interstrand cross-links (ICL). Fanconi anemia pathway–deficient cells are hypersensitive to DNA ICL–inducing drugs such as cisplatin. Conversely, hyperactivation of the Fanconi anemia pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the Fanconi anemia pathw...

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KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents.

Fanconi anemia (FA) is a rare genetic disease characterized by congenital defects, bone marrow failure, chromosomal instability, and cancer susceptibility. One hallmark of cells from FA patients is hypersensitivity to interstrand cross-linking agents, such as the chemotherapeutics cisplatin and mitomycin C (MMC). We have recently characterized a FANCD2/FANCI-associated nuclease, KIAA1018/FAN1, ...

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Deficiency of FANCD2-Associated Nuclease KIAA1018/FAN1 Sensitizes Cells to Interstrand Crosslinking Agents

Cytotoxicity of cisplatin and mitomycin C (MMC) is ascribed largely to their ability to generate interstrand crosslinks (ICLs) in DNA, which block the progression of replication forks. The processing of ICLs requires the Fanconi anemia (FA) pathway, excision repair, and translesion DNA synthesis (TLS). It also requires homologous recombination (HR), which repairs double-strand breaks (DSBs) gen...

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Interstrand cross-linking by adriamycin in nuclear and mitochondrial DNA of MCF-7 cells.

Activation of Adriamycin by formaldehyde leads to the formation of drug-DNA adducts in vitro and these adducts stabilise the DNA to such a degree that they function as virtual interstrand cross-links. The formation of these virtual interstrand cross-links by Adriamycin was investigated in MCF-7 cells using a gene-specific interstrand cross-linking assay. Cross-linking was measured in both the n...

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ژورنال

عنوان ژورنال: Molecular Cancer Research

سال: 2012

ISSN: 1541-7786,1557-3125

DOI: 10.1158/1541-7786.mcr-11-0497