title: ABH2 couples regulation of ribosomal DNA transcription with DNA alkylation repair.
abstract: Transcription has been linked to DNA damage. How the most highly transcribed mammalian ribosomal (rDNA) genes maintain genome integrity in the absence of transcription-coupled DNA damage repair is poorly understood. Here, we report that ABH2/ALKBH2, a DNA alkylation repair enzyme, is highly enriched in the nucleolus. ABH2 interacts with DNA repair proteins Ku70 and Ku80 as well as nucleolar proteins nucleolin, nucleophosmin 1, and upstream binding factor (UBF). ABH2 associates with and promotes rDNA transcription through its DNA repair activity. ABH2 knockdown impairs rDNA transcription and leads to increased single-stranded and double-stranded DNA breaks that are more pronounced in the rDNA genes, whereas ABH2 overexpression protects cells from methyl-methanesulfonate-induced DNA damage and inhibition of rDNA transcription. In response to massive alkylation damage, ABH2 rapidly redistributes from the nucleolus to nucleoplasm. Our study thus reveals a critical role of ABH2 in maintaining rDNA gene integrity and transcription and provides insight into the ABH2 DNA repair function.
authors: The Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors: Pishun
authors: P
authors: Li
authors: Shuman
authors: S
authors: Gao
authors: Lina
authors: L
authors: Wang
authors: Fang
authors: F
authors: Yu
authors: Jialun
authors: J
authors: Li
authors: Chuangui
authors: C
authors: Wang
authors: Jiwen
authors: J
authors: Li
authors: Jiemin
authors: J
authors: Wong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D000478:Alkylation; D034961:Antigens, Nuclear / Q000378:metabolism; D002466:Cell Nucleolus / Q000201:enzymology / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D059767:Recombinational DNA Repair; D014158:Transcription, Genetic; D000097796:Nucleolin
chemical_list: D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D034961:Antigens, Nuclear; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D049308:Dioxygenases; D000072200:Ku Autoantigen; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C000716967:NPM1 protein, human; C063844:transcription factor UBF; C486440:ALKBH2 protein, human; C000606509:Xrcc6 protein, human