Reactome | ERCC5 and RPA bind TC-NER site

ERCC5 and RPA bind TC-NER site

Stable Identifier

R-HSA-6782138

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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