title: Dephosphorylation of Orc2 by protein phosphatase 1 promotes the binding of the origin recognition complex to chromatin.
abstract: Phosphorylation of Orc2, one of the six subunits of the origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin and replication origins. Dephosphorylation of the phosphorylated Orc2 by protein phosphatase 1 (PP1) is accompanied by the binding of the dissociated subunits to chromatin. Here we show that PP1 physically interacts with Orc2. The binding of PP1 to Orc2 and the dephosphorylation of Orc2 by PP1 occurred in a cell cycle-dependent manner through an interaction with 119-KSVSF-123, which is the consensus motif for the binding of PP1, of Orc2. The dephosphorylation of Orc2 by PP1 is required for the binding of Orc2 to chromatin. These results support that PP1 dephosphorylates Orc2 to promote the binding of ORC to chromatin and replication origins for the subsequent round of the cell cycle.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyung Yong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: June Sung
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: dshwang@snu.ac.kr.
authors.forename: Deog Su
authors.initials: DS
authors.lastname: Hwang
mesh_terms: D019943:Amino Acid Substitution; D002453:Cell Cycle; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D051738:Origin Recognition Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D020798:Two-Hybrid System Techniques
chemical_list: D002843:Chromatin; C497224:ORC2 protein, human; D051738:Origin Recognition Complex; D011994:Recombinant Proteins; D054645:Protein Phosphatase 1
keywords: Cell cycle; DNA replication; Dephosphorylation; ORC; Protein phosphatase 1