@article{22c9e87dbd4a4bda8e5efb8ec0f94c9e,
title = "Genome-wide surveillance of transcription errors in response to genotoxic stress",
abstract = "Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.",
keywords = "DNA damage, Genotoxic stress, Mutagenesis, Transcription error",
author = "C. Fritsch and Gout, {J. F.} and S. Haroon and A. Towheed and C. Chung and J. LaGosh and E. McGann and X. Zhang and Y. Song and S. Simpson and Danthi, {P. S.} and Benayoun, {B. A.} and D. Wallace and K. Thomas and M. Lynch and M. Vermulst",
note = "Funding Information: ACKNOWLEDGMENTS. We thank the National Center for Genome Analysis Support (National Center for Genome Analysis Support; NSF ABI-1759906 2018) at Indiana University for access to their Mason Linux cluster, which was used to perform most of the analyses presented in this paper. This research was supported by the National Institute on Aging Award R01AG054641 (to M.V.), an American Federation for Aging Research young investigator award in Alzheimer{\textquoteright}s disease (to M.V.), the Multidisciplinary University Research Initiative Awards W911NF-09-1-0444 from the US Army Research Office (to M.L.), NIH Award R35-GM122566-01 (to M.L.), and Environmental Toxicology Training Grant T32ES019851 by the National Institute of Environmental Health Sciences (to C.F.). Funding Information: We thank the National Center for Genome Analysis Support (National Center for Genome Analysis Support; NSF ABI-1759906 2018) at Indiana University for access to their Mason Linux cluster, which was used to perform most of the analyses presented in this paper. This research was supported by the National Institute on Aging Award R01AG054641 (to M.V.), an American Federation for Aging Research young investigator award in Alzheimer's disease (to M.V.), the Multidisciplinary University Research Initiative Awards W911NF-09-1-0444 from the US Army Research Office (to M.L.), NIH Award R35-GM122566-01 (to M.L.), and Environmental Toxicology Training Grant T32ES019851 by the National Institute of Environmental Health Sciences (to C.F.).",
year = "2020",
doi = "10.1073/pnas.2004077118",
language = "English (US)",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "1",
}