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Inducing DNA damage through R-loops to kill cancer cells

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sword-2021-08-04T15:48:55.original.xml (130 B)
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Author(s)
Lam, Fred C
•
Kong, Yi Wen
•
Yaffe, Michael B
Date Issued
2021
Journal
Molecular and Cellular Oncology
Publisher
Informa UK Limited
Version
Final published version
Abstract
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. R-loops are intermediate structures of transcription that can accumulate when transcriptional elongation is blocked by inhibiting BRD4. In normal cells, R-loop persistence suppresses firing of adjacent replication origins. This control is lost in a subset of cancer cells, where BRD4 inhibition results in R-loop accumulation, leading to transcription-replication collisions and DNA double-strand breaks during S-phase, followed by cell death. This finding sheds new light on the mechanisms by which BRD4 inhibitors function as cancer therapies, and indicates that targeting other cellular events to cause R-loop accumulation may be useful for cancer treatment.
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DOI of Published Version
10.1080/23723556.2020.1848233
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