Topoisomerase IIalpha controls the decatenation checkpoint.
Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIalpha acts as a binding site for the BRCT domain of MDC1 (mediator of DNA damage checkpoint protein-1), thereby recruiting MDC1 to chromatin. Although Topo IIalpha-MDC1 interaction is not required for checkpoint activation induced by DNA damage, it is required for activation of the decatenation checkpoint. Mutation of Ser 1524 results in a defective decatenation checkpoint. These results reveal an important role of Topo II in checkpoint activation and in the maintenance of genomic stability.
Luo
Kuntian
K
Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Yuan
Jian
J
Chen
Junjie
J
Lou
Zhenkun
Z
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence / Q000235:genetics; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D018816:Genes, cdc / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D034741:RNA, Small Interfering; D012694:Serine / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D012694:Serine; D004250:DNA Topoisomerases, Type II