PMID:15215892

Citation	Prasanth, SG, Prasanth, KV, Siddiqui, K, Spector, DL and Stillman, B (2004) Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. EMBO J. 23:2651-63
Abstract	The initiation of DNA replication in S phase requires the prior assembly of an origin recognition complex (ORC)-dependent pre-replicative complex on chromatin during G1 phase of the cell division cycle. In human cells, the Orc2 subunit localized to the nucleus as expected, but it also localized to centrosomes throughout the entire cell cycle. Furthermore, Orc2 was tightly bound to heterochromatin and heterochromatin protein 1alpha (HP1alpha) and HP1beta in G1 and early S phase, but during late S, G2 and M phases tight chromatin association was restricted to centromeres. Depletion of Orc2 by siRNA caused multiple phenotypes. A population of cells showed an S-phase defect with little proliferating cell nuclear antigen (PCNA) on chromatin, although MCM proteins remained. Orc2 depletion also disrupted HP1 localization, but not histone-H3-lysine-9 methylation at prominent heterochromatic foci. Another subset of Orc2-depleted cells containing replicated DNA arrested with abnormally condensed chromosomes, failed chromosome congression and multiple centrosomes. These results implicate Orc2 protein in chromosome duplication, chromosome structure and centrosome copy number control, suggesting that it coordinates all stages of the chromosome inheritance cycle.
Links	PubMed PMC449767 Online version:10.1038/sj.emboj.7600255
Keywords	Apoptosis; Cell Cycle; Centromere/metabolism; Centrosome/metabolism; Chromatin/metabolism; Chromosomal Proteins, Non-Histone/metabolism; Chromosomes/genetics; Cloning, Molecular; DNA Replication; DNA-Binding Proteins/drug effects; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Flow Cytometry; Fluorescent Antibody Technique; HeLa Cells; Heterochromatin/metabolism; Humans; Kinetics; Metaphase; Origin Recognition Complex; Proliferating Cell Nuclear Antigen/genetics; Proliferating Cell Nuclear Antigen/metabolism; RNA, Small Interfering/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ORC2	part_of	GO:0005813: centrosome	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:ORC2		GO:0005813: centrosome	ECO:0000314:		C		Fig.1	complete CACAO 6978
HUMAN:ORC2		GO:0000792: heterochromatin	ECO:0000314:		C		Fig.2	complete CACAO 6979
HUMAN:ORC2	part_of	GO:0000792: heterochromatin	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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