Reactome | Assembly of the pre-incision complex in TC-NER

Assembly of the pre-incision complex in TC-NER

Stable Identifier

R-HSA-6782004

Type

Reaction

Species

Homo sapiens

Compartment

nucleoplasm

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Assembly of the pre-incision complex in TC-NER

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In addition to ERCC6 (CSB) and the ERCC8 (CSA) ubiquitin ligase complex, several other proteins and protein complexes are loaded onto stalled RNA polymerase II (RNA Pol II) at DNA damage sites to form a pre-incision complex that operates in the transcription-coupled nucleotide excision repair (TC-NER).
XPA, which also participates in global genome nucleotide excision repair (GG-NER), is necessary for the progression of TC-NER (Furuta et al. 2002). XPA interacts with the GTF2H5 subunit of the TFIIH complex (Ziani et al. 2014). In GG-NER, XPA loading is accompanied by the release of the CAK subcomplex from TFIIH (Coin et al. 2008), but in TC-NER the CAK complex remains bound to the TC-NER site (Mourgues et al. 2013).
XAB2 protein exists in the complex with five other proteins, AQR, PRPF19, ZNF830, ISY1 and PPIE. The XAB2 complex, which is also involved in pre-mRNA splicing, loads onto stalled RNA Pol II site (Kuraoka et al. 2008) through the interaction of XAB2 with RNA Pol II, ERCC6, ERCC8 and XPA (Nakatsu et al. 2000). The AQR (aquarius) subunit of the XAB2 complex is an RNA-DNA helicase that processes R-loops. An R-loop is a structure formed by hybridization of a nascent mRNA with a DNA template. In the absence of AQR, TC-NER machinery processes R-loops into double strand breaks (Sollier et al. 2014).
TCEA1 (TFIIS) is a transcription elongation factor that facilitates partial digestion of the 3' protruding end of the nascent transcript by a stalled RNA Pol II, which is generated during the reverse translocation of RNA Pol II from the damage site, and allows the resumption of RNA synthesis once the DNA damage is removed (Donahue et al. 1994).
HMGN1, a non-histone high mobility group N nucleosome-binding protein, facilitates TC-NER probably by increasing accessibility of damaged DNA to repair machinery. HMGN1 is recruited at RNA Pol II/TC-NER sites in an ERCC8 (CSA)-dependent manner (Birger et al. 2003, Fousteri et al. 2006).
Histone acetyltransferase p300 (EP300) is recruited to stalled RNA Pol II/TC-NER complexes in an ERCC6-dependent manner, and probably acts to facilitate access of repair proteins to damaged DNA via chromatin remodeling (Fousteri et al. 2006).
UVSSA protein forms a complex with ubiquitin protease USP7. It is recruited to TC-NER sites via interaction with ubiquitinated RNA Pol II and ERCC6. The UVSSA:USP7 complex stabilizes ERCC6, preventing its proteasome-mediated degradation prior to TC-NER completion, and may de-ubiquitinate RNA Pol II after TC-NER is completed, to allow resumption of RNA synthesis (Nakazawa et al. 2012, Schwertman et al. 2012, Zhang et al. 2012, Fei and Chen 2012).

Literature References

PubMed ID	Title	Journal	Year
12208738	Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells Pommier, Y, Sarasin, A, Aune, G, Ueda, T, Kraemer, KH, Furuta, T	Cancer Res.	2002
12660172	Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin Furusawa, T, Postnikov, YV, Wagner, JP, Birger, Y, Bustin, M, Lim, JH, Laufer, CS, Kraemer, KH, West, KL	EMBO J.	2003
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
9326587	Cockayne syndrome group B protein enhances elongation by RNA polymerase II Sancar, A, Selby, CP	Proc. Natl. Acad. Sci. U.S.A.	1997
22466610	Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair Kinoshita, A, Tateishi, S, Takenaka, K, Takahashi, Y, Yamashita, S, Lehmann, AR, Mishima, H, Masuyama, R, Nardo, T, Ohyama, K, Ito, K, Ogi, T, Stefanini, M, Ono, S, Yoshiura, K, Slor, H, Shimada, M, Mitsutake, N, Utani, A, Kudo, T, Matsuse, M, Sasaki, K, Nomura, M, Nakazawa, Y	Nat. Genet.	2012
24127601	ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair Coin, F, Monsarrat, B, Giglia-Mari, G, Mourgues, S, Mari, PO, Kaddoum, L, Bordier, C, Lagarou, A, Gautier, V, Mourcet, A, Slingerland, J, Gonzales de Peredo, A, Vermeulen, W	Proc. Natl. Acad. Sci. U.S.A.	2013
22466611	UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair Laffeber, C, Fousteri, M, Demmers, JA, Raams, A, van der Hoek, AC, Marteijn, JA, Lagarou, A, Schwertman, P, Dekkers, DH, Vermeulen, W, Hoeijmakers, JH	Nat. Genet.	2012
16916636	Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo Fousteri, M, Mullenders, LH, van Zeeland, AA, Vermeulen, W	Mol. Cell	2006
25435140	Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability Aguilera, A, Stork, CT, Cimprich, KA, García-Rubio, ML, Sollier, J, Paulsen, RD	Mol. Cell	2014
17981804	Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair Matsumoto, M, Kuraoka, I, Wada, T, Handa, H, Nakatani, Y, Lee, L, Qin, J, Tanaka, K, Nakatsu, Y, Saijo, M, Ito, S, Matsunaga, T, Hayashida, M	J. Biol. Chem.	2008
22902626	KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR) Fei, J, Chen, J	J. Biol. Chem.	2012
21070792	RNA interference against transcription elongation factor SII does not support its role in transcription-coupled nucleotide excision repair Mackinnon-Roy, C, Stubbert, LJ, McKay, BC	Mutat. Res.	2011
25154395	Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin Alekseev, S, Ziani, S, Coin, F, Egly, JM, Soutoglou, E, Nagy, Z	J. Cell Biol.	2014
18614043	Nucleotide excision repair driven by the dissociation of CAK from TFIIH Egly, JM, Oksenych, V, Coin, F, Groh, S, Blattner, C, Mocquet, V	Mol. Cell	2008
10944529	XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription Kamiuchi, S, Kodo, N, Yeo, JP, Matsuda, T, Vermeulen, W, Tanaka, K, Hoeijmakers, JH, Khaw, MC, Citterio, E, Saijo, M, Nakatsu, Y, Rademakers, S, Asahina, H	J. Biol. Chem.	2000