A topoisomerase II-dependent mechanism for resetting replicons at the S-M-phase transition.
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.
Cuvier
Olivier
O
Institute of Human Genetics, Centre National de la Recherche Scientifique (CNRS), Montpellier Cedex 5, France.
Stanojcic
Slavica
S
Lemaitre
Jean-Marc
JM
Mechali
Marcel
M
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015151:Immunoblotting; D008297:Male; D009154:Mutation; D009865:Oocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D012093:Replicon / Q000235:genetics / Q000502:physiology*; D000077546:Roscovitine; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D051738:Origin Recognition Complex; D011687:Purines; C102178:XOrc1 protein, Xenopus; D029867:Xenopus Proteins; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases; D004250:DNA Topoisomerases, Type II