Inducing DNA damage through R-loops to kill cancer cells
Name
Inducing DNA damage through R loops to kill cancer cells.pdf
Description
Published version
Size
1.01 MB
Format
Unknown
Checksum (MD5)
e9703c5b29c91a82c7ac4c1bf1d6673e
Author(s)
Lam, Fred Chiu-Lai
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.
MIT Department
Center for Precision Cancer Medicine
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1080/23723556.2020.1848233
