Cuvier Olivier, Stanojcic Slavica, Lemaitre Jean-Marc, Mechali Marcel
Institute of Human Genetics, Centre National de la Recherche Scientifique (CNRS), Montpellier Cedex 5, France.
Genes Dev. 2008 Apr 1;22(7):860-5. doi: 10.1101/gad.445108.
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.
拓扑异构酶II(topo II)对于染色体分离和复制子重编程是必需的。在此,我们表明topo II将DNA复制终止与复制复合物的清除相耦合,以便在有丝分裂时重置复制子。Topo II抑制会损害DNA复制的完成,这导致复制蛋白A(RPA)稳定在单链DNA上。Topo II抑制并不影响在复制起点激活时发现的对咖啡因敏感的ORC1降解,但它会损害有丝分裂时ORC1/2储备库的细胞周期蛋白依赖性激酶(cdk)依赖的降解/染色质解离。我们的结果表明,Pin1缺失可挽救ORC1降解,并且这种topo II依赖的从染色质清除ORC1/2涉及后期促进复合物(APC)。