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RNA polymerase II is released from the DNA template during transcription-coupled repair in mammalian cells.
J Biol Chem. 2018 02 16; 293(7):2476-2486.JB

Abstract

In mammalian cells, bulky DNA adducts located in the template but not the coding strand of genes block elongation by RNA polymerase II (RNAPII). The blocked RNAPII targets these transcription-blocking adducts to undergo more rapid excision repair than adducts located elsewhere in the genome. In excision repair, coupled incisions are made in the damaged DNA strand on both sides of the adduct. The fate of RNAPII in the course of this transcription-coupled repair (TCR) pathway is unclear. To address the fate of RNAPII, we used methods that control transcription to initiate a discrete "wave" of elongation complexes. Analyzing genome-wide transcription and repair by next-generation sequencing, we identified locations of elongation complexes and transcription-repair coupling events in genes throughout the genome. Using UV-exposed human skin fibroblasts, we found that, at the dose used, a single wave of elongation complexes was blocked within the first 25 kb of genes. TCR occurred where the elongation complexes were blocked, and repair was associated with the dissociation of these complexes. These results indicate that individual elongation complexes do not engage in multiple rounds of TCR with successive lesions. Our results are consistent with a model in which RNAPII is dissociated after the dual incision of the transcription-blocking lesion, perhaps by Cockayne syndrome group B translocase, or during the synthesis of a repair patch.

Authors+Show Affiliations

From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and. the Institute of Biochemistry, National Chung Hsing University, Taichung 402, Taiwan.From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and.From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and aziz_sancar@med.unc.edu.From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29282293

Citation

Chiou, Yi-Ying, et al. "RNA Polymerase II Is Released From the DNA Template During Transcription-coupled Repair in Mammalian Cells." The Journal of Biological Chemistry, vol. 293, no. 7, 2018, pp. 2476-2486.
Chiou YY, Hu J, Sancar A, et al. RNA polymerase II is released from the DNA template during transcription-coupled repair in mammalian cells. J Biol Chem. 2018;293(7):2476-2486.
Chiou, Y. Y., Hu, J., Sancar, A., & Selby, C. P. (2018). RNA polymerase II is released from the DNA template during transcription-coupled repair in mammalian cells. The Journal of Biological Chemistry, 293(7), 2476-2486. https://doi.org/10.1074/jbc.RA117.000971
Chiou YY, et al. RNA Polymerase II Is Released From the DNA Template During Transcription-coupled Repair in Mammalian Cells. J Biol Chem. 2018 02 16;293(7):2476-2486. PubMed PMID: 29282293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RNA polymerase II is released from the DNA template during transcription-coupled repair in mammalian cells. AU - Chiou,Yi-Ying, AU - Hu,Jinchuan, AU - Sancar,Aziz, AU - Selby,Christopher P, Y1 - 2017/12/27/ PY - 2017/11/16/received PY - 2017/12/19/revised PY - 2017/12/29/pubmed PY - 2019/2/6/medline PY - 2017/12/29/entrez KW - DNA damage KW - DNA repair KW - RNA polymerase II KW - gene transcription KW - nucleotide excision repair SP - 2476 EP - 2486 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 293 IS - 7 N2 - In mammalian cells, bulky DNA adducts located in the template but not the coding strand of genes block elongation by RNA polymerase II (RNAPII). The blocked RNAPII targets these transcription-blocking adducts to undergo more rapid excision repair than adducts located elsewhere in the genome. In excision repair, coupled incisions are made in the damaged DNA strand on both sides of the adduct. The fate of RNAPII in the course of this transcription-coupled repair (TCR) pathway is unclear. To address the fate of RNAPII, we used methods that control transcription to initiate a discrete "wave" of elongation complexes. Analyzing genome-wide transcription and repair by next-generation sequencing, we identified locations of elongation complexes and transcription-repair coupling events in genes throughout the genome. Using UV-exposed human skin fibroblasts, we found that, at the dose used, a single wave of elongation complexes was blocked within the first 25 kb of genes. TCR occurred where the elongation complexes were blocked, and repair was associated with the dissociation of these complexes. These results indicate that individual elongation complexes do not engage in multiple rounds of TCR with successive lesions. Our results are consistent with a model in which RNAPII is dissociated after the dual incision of the transcription-blocking lesion, perhaps by Cockayne syndrome group B translocase, or during the synthesis of a repair patch. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/29282293/RNA_polymerase_II_is_released_from_the_DNA_template_during_transcription_coupled_repair_in_mammalian_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=29282293 DB - PRIME DP - Unbound Medicine ER -