title: Topoisomerase II regulates the maintenance of DNA methylation.
abstract: The maintenance of DNA methylation in nascent DNA is a critical event for numerous biological processes. Following DNA replication, DNMT1 is the key enzyme that strictly copies the methylation pattern from the parental strand to the nascent DNA. However, the mechanism underlying this highly specific event is not thoroughly understood. In this study, we identified topoisomerase IIα (TopoIIα) as a novel regulator of the maintenance DNA methylation. UHRF1, a protein important for global DNA methylation, interacts with TopoIIα and regulates its localization to hemimethylated DNA. TopoIIα decatenates the hemimethylated DNA following replication, which might facilitate the methylation of the nascent strand by DNMT1. Inhibiting this activity impairs DNA methylation at multiple genomic loci. We have uncovered a novel mechanism during the maintenance of DNA methylation.
authors.affiliation: From the Women's Hospital, School of Medicine, and the Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China and lulinyu@zju.edu.cn.
authors.forename: Lin-Yu
authors.initials: LY
authors.lastname: Lu
authors.affiliation: the Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Henry
authors.initials: H
authors.lastname: Kuang
authors.affiliation: the Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Gautam
authors.initials: G
authors.lastname: Korakavi
authors.affiliation: the Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109 xiayu@umich.edu.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D011485:Protein Binding / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D004250:DNA Topoisomerases, Type II
keywords: DNA Demethylation; DNA Enzyme; DNA Methylation; DNA Methyltransferase; DNA Topoisomerase