Abstract
Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis1. 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 IIα 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 IIα–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.
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Acknowledgements
This work was supported in part by grants to J.C. from the National Institutes of Health (NIH). Z.L. was supported by grants from the Richard Schulze Family Foundation, Susan G. Komen Breast Cancer Foundation and NIH (CA130996). J.C. is a recipient of an Era of Hope Scholars award from the Department of Defense, and a member of the Mayo Clinic Breast SPORE program.
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K.L., J.Y. and Z.L. performed the experiments and analysed the data; Z.L. and J.C. wrote the paper. All authors discussed the results and commented on the manuscript.
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Luo, K., Yuan, J., Chen, J. et al. Topoisomerase IIα controls the decatenation checkpoint. Nat Cell Biol 11, 204–210 (2009). https://doi.org/10.1038/ncb1828
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DOI: https://doi.org/10.1038/ncb1828
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