Viral AlkB proteins repair RNA damage by oxidative demethylation

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Viral AlkB proteins repair RNA damage by oxidative demethylation

Bacterial and mammalian AlkB proteins are iron(II)- and 2-oxoglutarate-dependent dioxygenases that reverse methylation damage, such as 1-methyladenine and 3-methylcytosine, in RNA and DNA. An AlkB-domain is encoded by the genome of numerous single-stranded, plant-infecting RNA viruses, the majority of which belong to the Flexiviridae family. Our phylogenetic analysis of AlkB sequences suggests ...

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Oxidative dealkylation DNA repair mediated by the mononuclear non-heme iron AlkB proteins.

DNA can be damaged by various intracellular and environmental alkylating agents to produce alkylation base lesions. These base damages, if not repaired promptly, may cause genetic changes that lead to diseases such as cancer. Recently, it was discovered that some of the alkylation DNA base damage can be directly removed by a family of proteins called the AlkB proteins that utilize a mononuclear...

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Direct repair of the exocyclic DNA adduct 1,N6-ethenoadenine by the DNA repair AlkB proteins.

The exocyclic DNA base adduct 1,N6-ethenoadenine (epsilonA) is directly repaired by the AlkB proteins in vitro.

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RNA Repair: Damage Control

RNA in a cell is subject to many of the same insults as DNA. RNA damage can induce apoptosis and may be exploited for anti-cancer chemotherapy. It is a surprise, however, to learn that cells may repair RNA damage, suggesting a far greater significance of RNA in genotoxic stress.

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Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.

Methylating agents are ubiquitous in the environment, and central in cancer therapy. The 1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of such agents. These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli. Here, we report the structure of the hABH3 catalytic core in complex with iron and 2-oxoglutarate (2OG) at 1.5 A ...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 2008

ISSN: 1362-4962,0305-1048

DOI: 10.1093/nar/gkn519