title: Protein phosphatase 1 dephosphorylates Orc2.
abstract: Phosphorylation of Thr(116) and Thr(226) on 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. The phosphorylated Orc2 becomes dephosphorylated in the late M phase of the cell cycle. Here we show that protein phosphatase 1 (PP1) dephosphorylates Orc2. Dephosphorylation of Orc2 was accompanied by associating the dissociated Orc subunits with chromatin. Inhibitors of PP1 preferentially inhibited the dephosphorylation of Orc2. The overexpression of the α, β and γ PP1 isoforms decreased the amount of phosphorylated Orc2, and the depletion of these isoforms by RNA interference increased the amount of phosphorylated Orc2. These results suggest that PP1 dephosphorylates Orc2 to promote the binding of ORC to chromatin.
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: Gwang Su
authors.initials: GS
authors.lastname: Kim
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: D002843:Chromatin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D007527:Isoenzymes; C497224:ORC2 protein, human; D051738:Origin Recognition Complex; D013912:Threonine; D054645:Protein Phosphatase 1
keywords: Cell cycle; DNA replication; Dephosphorylation; ORC; Protein phosphatase 1