Dual incision in TC-NER

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R-HSA-6782135
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Pathway
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Homo sapiens
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In transcription-coupled nucleotide excision repair (TC-NER), similar to global genome nucleotide excision repair (GG-NER), the oligonucleotide that contains the lesion is excised from the open bubble structure via dual incision of the affected DNA strand. 5' incision by the ERCC1:ERCC4 (ERCC1:XPF) endonuclease precedes 3' incision by ERCC5 (XPG) endonuclease. In order for the TC-NER pre-incision complex to assemble and the endonucleases to incise the damaged DNA strand, the RNA polymerase II (RNA Pol II) complex has to backtrack - reverse translocate from the damage site. Although the mechanistic details of this process are largely unknown in mammals, it may involve ERCC6/ERCC8-mediated chromatin remodelling/ubiquitination events, the DNA helicase activity of the TFIIH complex and TCEA1 (TFIIS)-stimulated cleavage of the 3' protruding end of nascent mRNA by RNA Pol II (Donahue et al. 1994, Lee et al. 2002, Sarker et al. 2005, Vermeulen and Fousteri 2013, Hanawalt and Spivak 2008, Staresincic et al. 2009, Epshtein et al. 2014).

Literature References
PubMed ID Title Journal Year
11904382 Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro

Lee, KB, Wang, D, Lippard, SJ, Sharp, PA

Proc. Natl. Acad. Sci. U.S.A. 2002
23906714 Mammalian transcription-coupled excision repair

Vermeulen, W, Fousteri, M

Cold Spring Harb Perspect Biol 2013
24402227 UvrD facilitates DNA repair by pulling RNA polymerase backwards

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

Nature 2014
8078911 Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template

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

Proc. Natl. Acad. Sci. U.S.A. 1994
16246722 Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome

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

Mol. Cell 2005
19279666 Coordination of dual incision and repair synthesis in human nucleotide excision repair

Staresincic, L, Fagbemi, AF, Enzlin, JH, Gourdin, AM, Wijgers, N, Dunand-Sauthier, I, Giglia-Mari, G, Clarkson, SG, Vermeulen, W, Schärer, OD

EMBO J. 2009
19023283 Transcription-coupled DNA repair: two decades of progress and surprises

Hanawalt, PC, Spivak, G

Nat. Rev. Mol. Cell Biol. 2008
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