A novel role for transcription-coupled nucleotide excision repair for the in vivo repair of 3, N[superscript4]-ethenocytosine
Name
A novel role for transcription.pdf
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Author(s)
Iyama, Teruaki
Chaim, Isaac Alexander
Gardner, Alycia M.
Wu, Jie
Wilson, David M.
Samson, Leona D
Date Issued
January 2017
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Citation
Chaim, Isaac A., Alycia Gardner, Jie Wu, Teruaki Iyama, David M. Wilson, and Leona D. Samson. “A Novel Role for Transcription-Coupled Nucleotide Excision Repair for the in Vivo repair of 3,N[superscript 4]-Ethenocytosine.” Nucleic Acids Research (January 23, 2017): gkx015.
Version
Final published version
Abstract
Etheno (ε) DNA base adducts are highly mutagenic lesions produced endogenously via reactions with lipid peroxidation (LPO) products. Cancer-promoting conditions, such as inflammation, can induce persistent oxidative stress and increased LPO, resulting in the accumulation of ε-adducts in different tissues. Using a recently described fluorescence multiplexed host cell reactivation assay, we show that a plasmid reporter bearing a site-specific 3,N4-ethenocytosine (εC) causes transcriptional blockage. Notably, this blockage is exacerbated in Cockayne Syndrome and xeroderma pigmentosum patient-derived lymphoblastoid and fibroblast cells. Parallel RNA-Seq expression analysis of the plasmid reporter identifies novel transcriptional mutagenesis properties of εC. Our studies reveal that beyond the known pathways, such as base excision repair, the process of transcription-coupled nucleotide excision repair plays a role in the removal of εC from the genome, and thus in the protection of cells and tissues from collateral damage induced by inflammatory responses.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1093/nar/gkx015
