Pathway Human Homo sapiens

Formation of TC-NER Pre-Incision Complex

R-HSA-6781823 in Reactome release 97: under Transcription-Coupled Nucleotide Excision Repair (TC-NER), with 52 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-6781823 (mouse), R-RNO-6781823 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-6781823.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2004-03-06
Last updated: 2016-06-27
Events inside: 7, counted from the record

Formation of TC-NER pre-incision complex is initiated when the RNA polymerase II (RNA Pol II) complex stalls at a DNA damage site. The stalling is caused by misincorporation of a ribonucleotide opposite to a damaged base (Brueckner et al. 2007). Cockayne syndrome protein B (ERCC6, CSB) binds stalled RNA Pol II and recruits Cockayne syndrome protein A (ERCC8, CSA). ERCC8 is part of an ubiquitin ligase complex that also contains DDB1, CUL4A or CUL4B and RBX1. This complex is implicated in the regulation of TC-NER progression probably by ubiquitinating one or more factors involved in this pathway, which may include RNA Pol II and ERCC6 at the later stages of repair (Bregman et al. 1996, Fousteri et al. 2006, Groisman et al. 2006). XPA is recruited to the TC-NER site through its interaction with the TFIIH complex (Furuta et al. 2002, Ziani et al. 2014). The XAB2 complex, which probably regulates the accessibility of the DNA damage site through its RNA-DNA helicase activity, binds the TC-NER site via the interaction of its XAB2 subunit with RNA Pol II, ERCC6, ERCC8 and XPA (Nakatsu et al. 2000, Sollier et al. 2014). TCEA1 (TFIIS) is a transcription elongation factor that may facilitate backtracking of the stalled RNA Pol II, enabling access of repair proteins to the DNA damage site and promotes partial digestion of the 3' protruding end of the nascent mRNA transcript by the backtracked RNA Pol II, allowing resumption of RNA synthesis after damage removal (Donahue et al. 1994). Access to DNA damage sites in TC-NER was suggested to be facilitated by a chromatin remodeler HMGN1 (Birger et al. 2003), but another sudy found that HMGN1 was not needed for human TC-NER (Apelt et al. 2020). UVSSA protein interacts with ubiquitinated ERCC6 and RNA Pol II, recruiting ubiquitin protease USP7 to the TC-NER site and promoting ERCC6 stabilization (Nakazawa et al. 2012, Schwertman et al. 2012, Zhang et al. 2012, Fei and Chen 2012).

Literature Reactome attaches

CPD damage recognition by transcribing RNA polymerase IIScience, 2007, vol. 315, p. 859-62PubMed 17290000
UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cellsProc. Natl. Acad. Sci. U.S.A., 1996, vol. 93, p. 11586-90PubMed 8876179
CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndromeGenes Dev., 2006, vol. 20, p. 1429-34PubMed 16751180
Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cellsCancer Res., 2002, vol. 62, p. 4899-902PubMed 12208738
Sequential and ordered assembly of a large DNA repair complex on undamaged chromatinJ. Cell Biol., 2014, vol. 206, p. 589-98PubMed 25154395
XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcriptionJ. Biol. Chem., 2000, vol. 275, p. 34931-7PubMed 10944529
Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instabilityMol. Cell, 2014, vol. 56, p. 777-85PubMed 25435140
Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA templateProc. Natl. Acad. Sci. U.S.A., 1994, vol. 91, p. 8502-6PubMed 8078911
Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatinEMBO J., 2003, vol. 22, p. 1665-75PubMed 12660172
Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repairNat. Genet., 2012, vol. 44, p. 586-92PubMed 22466610
UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repairNat. Genet., 2012, vol. 44, p. 598-602PubMed 22466611
KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR)J. Biol. Chem., 2012, vol. 287, p. 35118-26PubMed 22902626
Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repairSci Rep, 2020, vol. 10, p. 4332PubMed 32152397

Reactome's record lists 14 orthologous events, R-MMU-6781823 (Mus musculus), R-RNO-6781823 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Formation of TC-NER Pre-Incision Complex". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-6781823 with StableID: R-HSA-6781823.4 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 52 genes in this human pathway; showing 1 to 52, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneAQR	AuthorityHGNC:29513	Mapping file id9716 NCBI file	EvidenceTAS
GeneCCNH	AuthorityHGNC:1594	Mapping file id902 NCBI file	EvidenceTAS
GeneCDK7	AuthorityHGNC:1778	Mapping file id1022 NCBI file	EvidenceTAS
GeneCOPS2	AuthorityHGNC:30747	Mapping file id9318 NCBI file	EvidenceTAS
GeneCOPS3	AuthorityHGNC:2239	Mapping file id8533 NCBI file	EvidenceTAS
GeneCOPS4	AuthorityHGNC:16702	Mapping file id51138 NCBI file	EvidenceTAS
GeneCOPS5	AuthorityHGNC:2240	Mapping file id10987 NCBI file	EvidenceTAS
GeneCOPS6	AuthorityHGNC:21749	Mapping file id10980 NCBI file	EvidenceTAS
GeneCOPS7A	AuthorityHGNC:16758	Mapping file id50813 NCBI file	EvidenceTAS
GeneCOPS7B	AuthorityHGNC:16760	Mapping file id64708 NCBI file	EvidenceTAS
GeneCOPS8	AuthorityHGNC:24335	Mapping file id10920 NCBI file	EvidenceTAS
GeneCUL4A	AuthorityHGNC:2554	Mapping file id8451 NCBI file	EvidenceTAS
GeneCUL4B	AuthorityHGNC:2555	Mapping file id8450 NCBI file	EvidenceTAS
GeneDDB1	AuthorityHGNC:2717	Mapping file id1642 NCBI file	EvidenceTAS
GeneERCC2	AuthorityHGNC:3434	Mapping file id2068 NCBI file	EvidenceTAS
GeneERCC3	AuthorityHGNC:3435	Mapping file id2071 NCBI file	EvidenceTAS
GeneERCC6	AuthorityHGNC:3438	Mapping file id2074 NCBI file	EvidenceTAS
GeneERCC8	AuthorityHGNC:3439	Mapping file id1161 NCBI file	EvidenceTAS
GeneGPS1	AuthorityHGNC:4549	Mapping file id2873 NCBI file	EvidenceTAS
GeneGTF2H1	AuthorityHGNC:4655	Mapping file id2965 NCBI file	EvidenceTAS
GeneGTF2H2	AuthorityHGNC:4656	Mapping file id2966 NCBI file	EvidenceTAS
GeneGTF2H3	AuthorityHGNC:4657	Mapping file id2967 NCBI file	EvidenceTAS
GeneGTF2H4	AuthorityHGNC:4658	Mapping file id2968 NCBI file	EvidenceTAS
GeneGTF2H5	AuthorityHGNC:21157	Mapping file id404672 NCBI file	EvidenceTAS
GeneISY1	AuthorityHGNC:29201	Mapping file id57461 NCBI file	EvidenceTAS
GeneISY1-RAB43	AuthorityHGNC:42969	Mapping file id100534599 NCBI file	EvidenceTAS
GeneMNAT1	AuthorityHGNC:7181	Mapping file id4331 NCBI file	EvidenceTAS
GenePOLR2A	AuthorityHGNC:9187	Mapping file id5430 NCBI file	EvidenceTAS
GenePOLR2B	AuthorityHGNC:9188	Mapping file id5431 NCBI file	EvidenceTAS
GenePOLR2C	AuthorityHGNC:9189	Mapping file id5432 NCBI file	EvidenceTAS
GenePOLR2D	AuthorityHGNC:9191	Mapping file id5433 NCBI file	EvidenceTAS
GenePOLR2E	AuthorityHGNC:9192	Mapping file id5434 NCBI file	EvidenceTAS
GenePOLR2F	AuthorityHGNC:9193	Mapping file id5435 NCBI file	EvidenceTAS
GenePOLR2G	AuthorityHGNC:9194	Mapping file id5436 NCBI file	EvidenceTAS
GenePOLR2H	AuthorityHGNC:9195	Mapping file id5437 NCBI file	EvidenceTAS
GenePOLR2I	AuthorityHGNC:9196	Mapping file id5438 NCBI file	EvidenceTAS
GenePOLR2J	AuthorityHGNC:9197	Mapping file id5439 NCBI file	EvidenceTAS
GenePOLR2K	AuthorityHGNC:9198	Mapping file id5440 NCBI file	EvidenceTAS
GenePOLR2L	AuthorityHGNC:9199	Mapping file id5441 NCBI file	EvidenceTAS
GenePPIE	AuthorityHGNC:9258	Mapping file id10450 NCBI file	EvidenceTAS
GenePRPF19	AuthorityHGNC:17896	Mapping file id27339 NCBI file	EvidenceTAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneTCEA1	AuthorityHGNC:11612	Mapping file id6917 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneUSP7	AuthorityHGNC:12630	Mapping file id7874 NCBI file	EvidenceTAS
GeneUVSSA	AuthorityHGNC:29304	Mapping file id57654 NCBI file	EvidenceTAS
GeneXAB2	AuthorityHGNC:14089	Mapping file id56949 NCBI file	EvidenceTAS
GeneXPA	AuthorityHGNC:12814	Mapping file id7507 NCBI file	EvidenceTAS
GeneZNF830	AuthorityHGNC:28291	Mapping file id91603 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Transcription-Coupled Nucleotide Excision Repair (TC-NER)R-HSA-678182777 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.