Inducing DNA damage through R-loops to kill cancer cells
© 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 ori...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Informa UK Limited
2021
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| Online Access: | https://hdl.handle.net/1721.1/133481 |
| _version_ | 1826199671638327296 |
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| author | Lam, Fred C Kong, Yi Wen Yaffe, Michael B |
| author_facet | Lam, Fred C Kong, Yi Wen Yaffe, Michael B |
| author_sort | Lam, Fred C |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T11:23:40Z |
| format | Article |
| id | mit-1721.1/133481 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:23:40Z |
| publishDate | 2021 |
| publisher | Informa UK Limited |
| record_format | dspace |
| spelling | mit-1721.1/1334812021-10-28T04:17:40Z Inducing DNA damage through R-loops to kill cancer cells Lam, Fred C Kong, Yi Wen Yaffe, Michael B © 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. 2021-10-27T19:53:04Z 2021-10-27T19:53:04Z 2021 2021-08-04T15:48:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133481 en 10.1080/23723556.2020.1848233 Molecular and Cellular Oncology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Informa UK Limited Taylor & Francis |
| spellingShingle | Lam, Fred C Kong, Yi Wen Yaffe, Michael B Inducing DNA damage through R-loops to kill cancer cells |
| title | Inducing DNA damage through R-loops to kill cancer cells |
| title_full | Inducing DNA damage through R-loops to kill cancer cells |
| title_fullStr | Inducing DNA damage through R-loops to kill cancer cells |
| title_full_unstemmed | Inducing DNA damage through R-loops to kill cancer cells |
| title_short | Inducing DNA damage through R-loops to kill cancer cells |
| title_sort | inducing dna damage through r loops to kill cancer cells |
| url | https://hdl.handle.net/1721.1/133481 |
| work_keys_str_mv | AT lamfredc inducingdnadamagethroughrloopstokillcancercells AT kongyiwen inducingdnadamagethroughrloopstokillcancercells AT yaffemichaelb inducingdnadamagethroughrloopstokillcancercells |