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Science 323 (5915): 789-793

Copyright © 2009 by the American Association for the Advancement of Science

Orc1 Controls Centriole and Centrosome Copy Number in Human Cells

Adriana S. Hemerly,1,2 Supriya G. Prasanth,1* Khalid Siddiqui,1{dagger} Bruce Stillman1{ddagger}

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.

1 Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor 11724, NY, USA.
2 Instituto de Bioquímica Médica, UFRJ, 21941-590, Rio de Janeiro, Brazil.

* Present address: Department of Cell and Developmental Biology, 601 South Goodwin Avenue, University of Illinois at Urbana–Champaign, Champaign, IL 61801, USA.

{dagger} Present address: Clare Hall Laboratories, Cancer Research UK, South Mimms, Herts, EN6 3LD, UK.

{ddagger} To whom correspondence should be addressed. E-mail: stillman{at}cshl.edu


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