title: DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation.
abstract: RNA-polymerase-I-dependent ribosomal DNA (rDNA) transcription is fundamental to rRNA processing, ribosome assembly and protein synthesis. However, how this process is initiated during the cell cycle is not fully understood. By performing a proteomic analysis of transcription factors that bind RNA polymerase I during rDNA transcription initiation, we identified that the DNA replication initiator Cdc6 interacts with RNA polymerase I and its co-factors, and promotes rDNA transcription in G1 phase in an ATPase-activity-dependent manner. We further showed that Cdc6 is targeted to the nucleolus during late mitosis and G1 phase in a manner that is dependent on B23 (also known as nucleophosmin, NPM1), and preferentially binds to the rDNA promoter through its ATP-binding domain. Overexpression of Cdc6 increases rDNA transcription, whereas knockdown of Cdc6 results in a decreased association of both RNA polymerase I and the RNA polymerase I transcription factor RRN3 with rDNA, and a reduction of rDNA transcription. Furthermore, depletion of Cdc6 impairs the interaction between RRN3 and RNA polymerase I. Taken together, our data demonstrate that Cdc6 also serves as a regulator of rDNA transcription initiation, and indicate a mechanism by which initiation of rDNA transcription and DNA replication can be coordinated in cells.
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Shijiao
authors.initials: S
authors.lastname: Huang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Guopeng
authors.initials: G
authors.lastname: Wang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Lu
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Xie
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Cancer Research Center, Peking University Hospital, Peking University, Beijing 100871, China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China zhangcm@pku.edu.cn.
authors.forename: Chuanmao
authors.initials: C
authors.lastname: Zhang
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009697:Nucleolus Organizer Region / Q000235:genetics; D000090243:Nucleophosmin; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000378:metabolism*; D061785:Transcription Initiation, Genetic / Q000502:physiology*
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; C428423:RRN3 protein, human; D000090243:Nucleophosmin; D012318:RNA Polymerase I
keywords: Cdc6; Cell cycle; Nucleophosmin; RNA polymerase I; RRN3; rDNA transcription