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, M
Herrero-Ruíz, A
Anderson, RM
Caldecott, K
Issue Date: 2017
Citation: Nature Communications, 8, 2017
Abstract: 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: http://bura.brunel.ac.uk/handle/2438/15019
DOI: http://dx.doi.org/10.1038/s41467-017-00307-y
ISSN: 2041-1723
Appears in Collections:Dept of Life Sciences Research Papers

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