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BRCA1 participates in DNA decatenation

Nature Structural & Molecular Biology volume 12, pages 589–593 (2005)Cite this article

Abstract

The tumor suppressor BRCA1 has an important function in the maintenance of genomic stability. Increasing evidence suggests that BRCA1 regulates cell cycle checkpoints and DNA repair after DNA damage. However, little is known about its normal function in the absence of DNA damage. Here we show that BRCA1 interacts and colocalizes with topoisomerase IIα in S phase cells. Similar to cells treated with the topoisomerase IIα inhibitor ICRF-193, BRCA1-deficient cells show lagging chromosomes, indicating a defect in DNA decatenation and chromosome segregation. More directly, BRCA1 deficiency results in defective DNA decatenation in vitro. Finally, topoisomerase IIα is ubiquitinated in a BRCA1-dependent manner, and topoisomerase IIα ubiquitination correlates with higher DNA decatenation activity. Together these results suggest an important role of BRCA1 in DNA decatenation and reveal a previously unknown function of BRCA1 in the maintenance of genomic stability.

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Figure 1: BRCA1 colocalizes and interacts with topoisomerase IIα.
Figure 2: Absence of BRCA1 results in defective chromosome segregation.
Figure 3: Absence of BRCA1 results in defective chromosome condensation.
Figure 4: BRCA1 is involved in DNA decatenation in vitro.
Figure 5: Topoisomerase IIα (Topo II) is ubiquitinated in a BRCA1-dependent manner.

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Acknowledgements

We thank R. Baer (Columbia University) for assisting us with the ubiquitination assay and J. Wood for providing suggestions and proofreading of this manuscript. This work is supported by grants from US National Institutes of Health (NIH RO1 CA89239 and CA92312 to J.C.). J.C. is a recipient of a Department of Defense (DOD) breast cancer career development award (DAMD17-02-1-0472). Z.L. is a recipient of a DOD breast cancer fellowship award (DAMD17-03-1-0610).

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  1. Department of Oncology, Mayo Clinic and Foundation, Rochester, 55905, Minnesota, USA

    Zhenkun Lou, Katherine Minter-Dykhouse & Junjie Chen

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Correspondence to Junjie Chen.

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Lou, Z., Minter-Dykhouse, K. & Chen, J. BRCA1 participates in DNA decatenation. Nat Struct Mol Biol 12, 589–593 (2005). https://doi.org/10.1038/nsmb953

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