A novel role for transcription-coupled nucleotide excision repair for the in vivo repair of 3, N[superscript4]-ethenocytosine

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 ti...

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Main Authors: Iyama, Teruaki (Author), Chaim, Isaac Alexander (Contributor), Gardner, Alycia M. (Contributor), Wu, Jie (Contributor), Wilson, David M. (Contributor), Samson, Leona D (Contributor)
Other Authors: Massachusetts Institute of Technology. Center for Environmental Health Sciences (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor)
Format: Article
Language:English
Published: Oxford University Press, 2017-06-21T16:06:33Z.
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Online Access:Get fulltext
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100 1 0 |a Iyama, Teruaki  |e author 
100 1 0 |a Massachusetts Institute of Technology. Center for Environmental Health Sciences  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Biological Engineering  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Chaim, Isaac Alexander  |e contributor 
100 1 0 |a Gardner, Alycia M.  |e contributor 
100 1 0 |a Wu, Jie  |e contributor 
100 1 0 |a Wilson, David M.  |e contributor 
100 1 0 |a Samson, Leona D  |e contributor 
700 1 0 |a Chaim, Isaac Alexander  |e author 
700 1 0 |a Gardner, Alycia M.  |e author 
700 1 0 |a Wu, Jie  |e author 
700 1 0 |a Wilson, David M.  |e author 
700 1 0 |a Samson, Leona D  |e author 
245 0 0 |a A novel role for transcription-coupled nucleotide excision repair for the in vivo repair of 3, N[superscript4]-ethenocytosine 
260 |b Oxford University Press,   |c 2017-06-21T16:06:33Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/110126 
520 |a 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. 
520 |a National Institutes of Health (U.S.) (Directors Pioneer Award [DPI-ES022576]) 
520 |a National Institutes of Health (U.S.) (R01-CA075576) 
520 |a National Institutes of Health (U.S.) (R01-CA55042) 
520 |a National Institutes of Health (U.S.) (R01-CA149261) 
520 |a National Institutes of Health (U.S.) (P30-ES02109) 
520 |a National Institutes of Health (U.S.). Intramural Research Program 
520 |a National Institute on Aging 
520 |a LDS discretionary funds 
546 |a en_US 
655 7 |a Article 
773 |t Nucleic Acids Research