ERCC3-facilitated RNA Pol II backtracking in TC-NER

Stable Identifier
Reaction [transition]
Homo sapiens
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The DNA helicase XPB (ERCC3), which is part of the TFIIH complex, unwinds the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site. ERCC3 is a 3'->5' directed DNA helicase whose ATPase activity, together with the 5'->3 directed helicase activity of ERCC2 (Kuper et al. 2012), contributes to dsDNA unwinding during nucleotide excision repair (NER) (Coin et al. 2007). In transcription-coupled NER (TC-NER), the ATPase activity of TFIIH complex, related to its helicase activity, is in addition necessary for the incision of the damaged DNA strand. While the endonuclease ERCC5 (XPG) can bind stalled RNA polymerase II (RNA Pol II) at a transcription bubble, it cannot perform incision in the absence of the TFIIH ATPase activity (Sarker et al. 2005). The helicase activity of the TFIIH complex may allow backtracking of the RNA Pol II, similar to the UvrD helicase involved in TC-NER in E.coli. Pulling RNA Pol II backwards from the DNA damage site would resolve steric hindrance of the RNA Pol II complex with the TC-NER endonucleases (Epshtein et al. 2014). RNA Pol II backtracking is accompanied by a partial digestion of the nascent 3' protruding mRNA via the 3'->5' directed exonuclease activity of RNA Pol II, which is stimulated by TCEA1 (TFIIS) (Donahue et al. 1994). Partial transcript digestion and RNA Pol II backtracking move the transcription bubble away from the open bubble that contains the DNA damage site (reviewed by Hanawalt and Spivak 2008).
Literature References
PubMed ID Title Journal Year
8078911 Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template

Donahue, BA, Reines, D, Taylor, JS, Yin, S, Hanawalt, PC

Proc. Natl. Acad. Sci. U.S.A. 1994
17466626 Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair

Oksenych, V, Coin, F, Egly, JM

Mol. Cell 2007
24402227 UvrD facilitates DNA repair by pulling RNA polymerase backwards

Ueberheide, B, Kamarthapu, V, Nudler, E, Proshkin, S, McGary, K, Mironov, A, Epshtein, V, Svetlov, V

Nature 2014
16246722 Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome

Kostek, S, Tainer, JA, Sarker, AH, Ng, C, Nogales, E, Cooper, PK, Campeau, E, Tsutakawa, SE, Peris, M, Shin, DS

Mol. Cell 2005
22081108 Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation

Michels, G, Wolski, SC, Kuper, J, Kisker, C

EMBO J. 2012
Catalyst Activity

3'-5' DNA helicase activity of TC-NER pre-incision complex:Partially open bubble damaged DNA template:trimmed nascent mRNA [nucleoplasm]

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