Topoisomerase IIα controls the decatenation checkpoint

Kuntian Luo; Jian Yuan; Junjie Chen; Zhenkun Lou

doi:10.1038/ncb1828

Topoisomerase IIα controls the decatenation checkpoint

Kuntian Luo, Jian Yuan, Junjie Chen, Zhenkun Lou

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

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 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.

Original language	English (US)
Pages (from-to)	204-210
Number of pages	7
Journal	Nature Cell Biology
Volume	11
Issue number	2
DOIs	https://doi.org/10.1038/ncb1828
State	Published - 2009

ASJC Scopus subject areas

Cell Biology

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10.1038/ncb1828

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title = "Topoisomerase IIα controls the decatenation checkpoint",

abstract = "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 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.",

author = "Kuntian Luo and Jian Yuan and Junjie Chen and Zhenkun Lou",

note = "Funding Information: 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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AU - Luo, Kuntian

AU - Yuan, Jian

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AU - Lou, Zhenkun

N1 - Funding Information: 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.

PY - 2009

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N2 - 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 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.

AB - 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 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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Topoisomerase IIα controls the decatenation checkpoint

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