Journal article
Topoisomerase IIa is essential for maintenance of mitotic chromosome structure
CF Nielsen, T Zhang, M Barisic, P Kalitsis, DF Hudson
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2020
Abstract
Topoisomerase IIα (TOP2A) is a core component of mitotic chromosomes and important for establishing mitotic chromosome condensation. The primary roles of TOP2A in mitosis have been difficult to decipher due to its multiple functions across the cell cycle. To more precisely understand the role of TOP2A in mitosis, we used the auxin-inducible degron (AID) system to rapidly degrade the protein at different stages of the human cell cycle. Removal of TOP2A prior to mitosis does not affect prophase timing or the initiation of chromosome condensation. Instead, it prevents chromatin condensation in prometaphase, extends the length of prometaphase, and ultimately causes cells to exit mitosis without ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
The authors thank Dr. Matthew Burton for providing flow cytometry and microscopy technical support. This work was supported by National Health and Medical Research Council Project Grants GNT1127209 and GNT145188, by the Victorian Government's Operational Infrastructure Support Program, The Danish National Research Foundation (DNRF115), and a Carlsberg Foundation Fellowship (CF16-0206). We thank members of the D.F.H., P.K., and Hickson laboratories for helpful discussions. Special thanks to Professor Ian D. Hickson, Professor Bill C. Earnshaw, Dr. Kumiko Samejima, and Dr. Kata Sarlos for critical feedback on the manuscript.