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Topoisomerase IIα controls the decatenation checkpoint

Nature Cell Biology volume 11, pages 204–210 (2009)Cite this article

An Author Correction to this article was published on 04 September 2018

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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Figure 1: MDC1 interacts with Topo IIα through its BRCT domain.
Figure 2: The pSer 1524 site of Topo IIα is the binding site of the MDC1 BRCT domain.
Figure 3: The MDC1–Topo IIα interaction is important for activation of the decatenation checkpoint.
Figure 4: Phospho-Topo IIα recruits MDC1 to chromatin and activates the decatenation checkpoint.

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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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Authors and Affiliations

  1. Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, 55905, MN, USA

    Kuntian Luo, Jian Yuan & Zhenkun Lou

  2. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, 06520, CT, USA

    Junjie Chen

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  1. Kuntian Luo
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Contributions

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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Correspondence to Junjie Chen or Zhenkun Lou.

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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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