AP endonucleases process 5-methylcytosine excision intermediates duringactive DNA demethylation in Arabidopsis
| Autor: | Hosung Jang, Jin Hoe Huh, Hosub Shin, Jiyoon Lee, Woo Lee Choi, Young Geun Mok |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
DNA Repair
DNA Plant DNA repair Arabidopsis DNA Glycosylases Endonuclease chemistry.chemical_compound DNA-(Apurinic or Apyrimidinic Site) Lyase Genetics N-Glycosyl Hydrolases biology Arabidopsis Proteins Gene regulation Chromatin and Epigenetics Nuclear Proteins Base excision repair Endonucleases Phosphoric Monoester Hydrolases Chromatin DNA demethylation Biochemistry chemistry DNA glycosylase Mutation 5-Methylcytosine Trans-Activators biology.protein DNA Nucleotide excision repair |
| Zdroj: | NUCLEIC ACIDS RESEARCH(42): 18 Nucleic Acids Research |
| Popis: | DNA methylation is a primary epigenetic modification regulating gene expression and chromatin structure in many eukaryotes. Plants have a unique DNA demethylation system in that 5-methylcytosine (5mC) is directly removed by DNA demethylases, such as DME/ROS1 family proteins, but little is known about the downstream events. During 5mC excision, DME produces 3'-phosphor-alpha, beta-unsaturated aldehyde and 3'-phosphate by successive beta-and delta-eliminations, respectively. The kinetic studies revealed that these 3'-blocking lesions persist for a significant amount of time and at least two different enzyme activities are required to immediately process them. We demonstrate that Arabidopsis AP endonucleases APE1L, APE2 and ARP have distinct functions to process such harmful lesions to allow nucleotide extension. DME expression is toxic to E. coli due to excessive 5mC excision, but expression of APE1L or ARP significantly reduces DME-induced cytotoxicity. Finally, we propose a model of base excision repair and DNA demethylation pathway unique to plants. |
| Databáze: | OpenAIRE |
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