Genome-wide surveillance of transcription errors in response to genotoxic stress

C. Fritsch, J. F. Gout, S. Haroon, A. Towheed, C. Chung, J. LaGosh, E. McGann, X. Zhang, Y. Song, S. Simpson, P. S. Danthi, B. A. Benayoun, D. Wallace, K. Thomas, M. Lynch, M. Vermulst

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere2004077118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number1
DOIs
StatePublished - 2020

Keywords

  • DNA damage
  • Genotoxic stress
  • Mutagenesis
  • Transcription error

ASJC Scopus subject areas

  • General

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