Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/15019
Title: | TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription |
Authors: | Gomez-Herreros, F Zagnoli-Vieira, G Ntai, I Martínez Macías, MI Herrero-Ruíz, A Anderson, RM Caldecott, K |
Keywords: | cancer genomics;chromosomes;DNA damage and repair |
Issue Date: | 10-Aug-2017 |
Citation: | Gómez-Herreros, F., Zagnoli-Vieira, G., Ntai, I., Martínez-Macías, M.I., Anderson, R.M., Herrero-Ruíz, A. and Caldecott, K.W. (2017) 'TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription', Nature Communications, 8, 233, pp. 1-9. doi: 10.1038/s41467-017-00307-y. |
Abstract: | © The Author(s) 2017. DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability. |
URI: | https://bura.brunel.ac.uk/handle/2438/15019 |
DOI: | https://doi.org/10.1038/s41467-017-00307-y |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FullText.pdf | 1.08 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License