ERCC5 and RPA bind TC-NER site

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

It has been suggested that, similar to the UvrD helicase involved in TC-NER in E.coli, the DNA helicase activity of TFIIH complex may facilitate damage-stalled RNA polymerase II (RNA Pol II) backtracking (Epshtein et al. 2014). RNA Pol II backtracking, together with the cleavage of the 3' protruding end of nascent mRNA, might promote the movement of the transcription bubble away from the transcription-coupled nucleotide excision repair (TC-NER) site, while an open bubble is created (Sarker et al. 2005, Hanawalt and Spivak 2008). Once the open bubble is generated, the RPA heterotrimer composed of RPA1, RPA2 and RPA3 coats the undamaged single strand DNA (ssDNA) (de Laat et al. 1998), thereby protecting it from endonucleases. The interaction of RPA with XPA facilitates RPA recruitment to the nucleotide excision repair (NER) site (He et al. 1995, Ikegami et al. 1998). A DNA endonuclease ERCC5 (XPG) is recruited to the TC-NER site through its interaction with the stalled RNA Pol II (Sarker et al. 2005), the TFIIH complex (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Ito et al. 2007) and the RPA heterotrimer (de Laat et al. 1998).

Literature References
PubMed ID Title Journal Year
9716411 DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair

Jaspers, NG, Appeldoorn, E, Weterings, E, Sugasawa, K, de Laat, WL, Hoeijmakers, JH

Genes Dev. 1998
7700386 RPA involvement in the damage-recognition and incision steps of nucleotide excision repair

Ingles, CJ, Wold, MS, He, Z, Henricksen, LA

Nature 1995
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
17000769 Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH

Houtsmuller, AB, van Cappellen, WA, van Driel, R, Luijsterburg, MS, Nigg, A, Zotter, A, Ibrahim, S, Vermeulen, W, Hoeijmakers, JH, Warmerdam, DO

Mol. Cell. Biol. 2006
9699634 Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA

Kodo, N, Ikegami, T, Saijo, M, Kyogoku, Y, Kuraoka, I, Morikawa, K, Shirakawa, M, Tanaka, K

Nat. Struct. Biol. 1998
17466625 XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients

Kuraoka, I, Tanaka, K, Compe, E, Ito, S, Coin, F, Ishigami, C, Egly, JM, Chymkowitch, P, Takedachi, A

Mol. Cell 2007
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
15590680 The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity

Hohl, M, Schärer, OD, Dunand-Sauthier, I, Thorel, F, Clarkson, SG, Jaquier-Gubler, P

J. Biol. Chem. 2005
Orthologous Events
Cite Us!