4.8 Article

Orc1 Controls Centriole and Centrosome Copy Number in Human Cells

Journal

SCIENCE
Volume 323, Issue 5915, Pages 789-793

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1166745

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Funding

  1. National Institutes of Health [CA13106]
  2. CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
  3. Leukemia and Lymphoma Society

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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.

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