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RESEARCH COMMUNICATION

A topoisomerase II-dependent mechanism for resetting replicons at the S–M-phase transition

Institute of Human Genetics, Centre National de la Recherche Scientifique (CNRS), Montpellier Cedex 5, France

Topoisomerase II (topo II) is required for chromosome segregation and for reprogramming replicons. Here, we show that topo II couples DNA replication termination with the clearing of replication complexes for resetting replicons at mitosis. Topo II inhibition impairs completion of DNA replication, accounting for replication protein A (RPA) stabilization onto ssDNA. Topo II inhibition does not affect the caffeine-sensitive ORC1 degradation found upon origin firing, but it impairs the cdk-dependent degradation/chromatin dissociation of an ORC1/2 reservoir at mitosis. Our results show that ORC1 degradation is rescued by Pin1 depletion and that this topo II-dependent clearing of ORC1/2 from chromatin involves the APC.

[Keywords: DNA replication origins; DNA replication foci; checkpoint; ICRF; ORC; DNA combing]]

Received June 18, 2007; revised version accepted January 30, 2008.

² Corresponding author.

E-MAIL mechali{at}igh.cnrs.fr; FAX 33-4-99-61-99-20.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.445108.

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