title: Orc1 controls centriole and centrosome copy number in human cells.
abstract: Centrosomes, each containing a pair of centrioles, organize microtubules in animal cells, particularly during mitosis. DNA and centrosomes are normally duplicated once before cell division to maintain optimal genome integrity. We report a new role for the Orc1 protein, a subunit of the origin recognition complex (ORC) that is a key component of the DNA replication licensing machinery, in controlling centriole and centrosome copy number in human cells, independent of its role in DNA replication. Cyclin A promotes Orc1 localization to centrosomes where Orc1 prevents Cyclin E-dependent reduplication of both centrioles and centrosomes in a single cell division cycle. The data suggest that Orc1 is a regulator of centriole and centrosome reduplication as well as the initiation of DNA replication.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor 11724, NY, USA.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Hemerly
authors.forename: Supriya G
authors.initials: SG
authors.lastname: Prasanth
authors.forename: Khalid
authors.initials: K
authors.lastname: Siddiqui
authors.forename: Bruce
authors.initials: B
authors.lastname: Stillman
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D002502:Centrioles / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004261:DNA Replication; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D050505:Mutant Proteins / Q000378:metabolism; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D019925:Cyclin A; D019927:Cyclin E; D050505:Mutant Proteins; C497223:ORC1 protein, human; D051738:Origin Recognition Complex; D034741:RNA, Small Interfering; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2