title: Two subunits of human ORC are dispensable for DNA replication and proliferation.
abstract: The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles ofORC2or of the ATPase subunit,ORC1. TheORC1orORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Shibata
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Manjari
authors.initials: M
authors.lastname: Kiran
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Samarendra
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Shashi
authors.initials: S
authors.lastname: Kiran
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Anindya
authors.identifier: 0000-0002-4319-0073
authors.initials: A
authors.lastname: Dutta
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D018741:Replication Origin
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C497223:ORC1 protein, human; C497224:ORC2 protein, human; D051738:Origin Recognition Complex; D004247:DNA; D064110:Minichromosome Maintenance Proteins
keywords: CDC6; DNA replication; ORC; cell biology; human