Nucleotide Excision Repair (Homo sapiens)
From WikiPathways
Description
NER was first described in the model organism E. coli in the early 1960s as a process whereby bulky base damage is enzymatically removed from DNA, facilitating the recovery of DNA synthesis and cell survival. Deficient NER processes have been identified from the cells of cancer-prone patients with different variants of xeroderma pigmentosum (XP), trichothiodystrophy (TTD), and Cockayne’s syndrome. These XP cells exhibited an ultraviolet radiation hypersensitivity leading to a hypermutability response to UV, offering a direct connection between deficient NER, increased mutations, and cancer. While the NER pathway in prokaryotes is unique, the pathway utilized in yeast and higher eukaryotes is highly conserved and includes a variety of proteins that interact to form complexes.
NER is involved in the repair of bulky adducts in DNA, such as UV-induced photo lesions [of both 6-4 photoproducts (6-4 pps) and cyclobutane pyrimidine dimer (CPDs)], intrastrand cross-links, large chemical adducts formed from exposure to aflatoxin, benzopyrene and other genotoxic agents. Specific proteins have been identified that participate in base damage recognition, cleavage of the damaged strand on both sides of the lesion, excision of the oligonucleotide bearing the lesion, and accessory proteins necessary for efficient function. Polymerization and ligation restore the strand to its original state. NER consists of two related pathways called global genomic repair (GG-NER) and transcription-coupled NER (TC-NER). The pathways differ in the way in which DNA damage is initially recognized, but the majority of the participating molecules are shared between these two branches of NER". GG-NER is considered to be transcription-independent, removing lesions from non-transcribed regions of genome in addition to non-transcribed strands of transcribed regions. The preferential repair of UV-induced damage in transcribed strands of active genes is known as Transcription-coupled NER (TC-NER).
Several of the proteins involved in NER are key components of the basal transcription complex TFIIH. NER proteins have also been shown to interact with the 19S regulatory subunit of the proteasome, suggesting a role in cellular regulation signal pathways. The establishment of mutant mouse models for NER genes and other DNA repair-related genes have been useful in demonstrating the associations between NER defects and cancer.
Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=73885
NER is involved in the repair of bulky adducts in DNA, such as UV-induced photo lesions [of both 6-4 photoproducts (6-4 pps) and cyclobutane pyrimidine dimer (CPDs)], intrastrand cross-links, large chemical adducts formed from exposure to aflatoxin, benzopyrene and other genotoxic agents. Specific proteins have been identified that participate in base damage recognition, cleavage of the damaged strand on both sides of the lesion, excision of the oligonucleotide bearing the lesion, and accessory proteins necessary for efficient function. Polymerization and ligation restore the strand to its original state. NER consists of two related pathways called global genomic repair (GG-NER) and transcription-coupled NER (TC-NER). The pathways differ in the way in which DNA damage is initially recognized, but the majority of the participating molecules are shared between these two branches of NER". GG-NER is considered to be transcription-independent, removing lesions from non-transcribed regions of genome in addition to non-transcribed strands of transcribed regions. The preferential repair of UV-induced damage in transcribed strands of active genes is known as Transcription-coupled NER (TC-NER).
Several of the proteins involved in NER are key components of the basal transcription complex TFIIH. NER proteins have also been shown to interact with the 19S regulatory subunit of the proteasome, suggesting a role in cellular regulation signal pathways. The establishment of mutant mouse models for NER genes and other DNA repair-related genes have been useful in demonstrating the associations between NER defects and cancer.
Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=73885
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Ontology Terms
Bibliography
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- Riedl T, Hanaoka F, Egly JM.; ''The comings and goings of nucleotide excision repair factors on damaged DNA.''; PubMed Europe PMC Scholia
- Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, Tanaka K, Shirakawa M.; ''Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA.''; PubMed Europe PMC Scholia
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- Min JH, Pavletich NP.; ''Recognition of DNA damage by the Rad4 nucleotide excision repair protein.''; PubMed Europe PMC Scholia
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- Sollier J, Stork CT, García-Rubio ML, Paulsen RD, Aguilera A, Cimprich KA.; ''Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability.''; PubMed Europe PMC Scholia
- Mourgues S, Gautier V, Lagarou A, Bordier C, Mourcet A, Slingerland J, Kaddoum L, Coin F, Vermeulen W, Gonzales de Peredo A, Monsarrat B, Mari PO, Giglia-Mari G.; ''ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair.''; PubMed Europe PMC Scholia
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- Fei J, Chen J.; ''KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR).''; PubMed Europe PMC Scholia
- Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F.; ''Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning.''; PubMed Europe PMC Scholia
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- Akita M, Tak YS, Shimura T, Matsumoto S, Okuda-Shimizu Y, Shimizu Y, Nishi R, Saitoh H, Iwai S, Mori T, Ikura T, Sakai W, Hanaoka F, Sugasawa K.; ''SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair.''; PubMed Europe PMC Scholia
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- Donahue BA, Yin S, Taylor JS, Reines D, Hanawalt PC.; ''Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template.''; PubMed Europe PMC Scholia
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- Moser J, Volker M, Kool H, Alekseev S, Vrieling H, Yasui A, van Zeeland AA, Mullenders LH.; ''The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions.''; PubMed Europe PMC Scholia
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- Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F.; ''Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
- Perez-Oliva AB, Lachaud C, Szyniarowski P, Muñoz I, Macartney T, Hickson I, Rouse J, Alessi DR.; ''USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage responses.''; PubMed Europe PMC Scholia
- Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMed Europe PMC Scholia
- Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura K, Ogi T.; ''Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair.''; PubMed Europe PMC Scholia
- Wittschieben BØ, Iwai S, Wood RD.; ''DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.''; PubMed Europe PMC Scholia
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- He Z, Henricksen LA, Wold MS, Ingles CJ.; ''RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.''; PubMed Europe PMC Scholia
- Volker M, Moné MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH.; ''Sequential assembly of the nucleotide excision repair factors in vivo.''; PubMed Europe PMC Scholia
- Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapić-Otrin V, Levine AS.; ''The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.''; PubMed Europe PMC Scholia
- Hofmann RM, Pickart CM.; ''Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.''; PubMed Europe PMC Scholia
- Sarkar S, Kiely R, McHugh PJ.; ''The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair.''; PubMed Europe PMC Scholia
- Mocquet V, Lainé JP, Riedl T, Yajin Z, Lee MY, Egly JM.; ''Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step.''; PubMed Europe PMC Scholia
- Mathieu N, Kaczmarek N, Rüthemann P, Luch A, Naegeli H.; ''DNA quality control by a lesion sensor pocket of the xeroderma pigmentosum group D helicase subunit of TFIIH.''; PubMed Europe PMC Scholia
- Giglia-Mari G, Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W.; ''A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A.''; PubMed Europe PMC Scholia
- Fischer ES, Scrima A, Böhm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thomä NH.; ''The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation.''; PubMed Europe PMC Scholia
- Staresincic L, Fagbemi AF, Enzlin JH, Gourdin AM, Wijgers N, Dunand-Sauthier I, Giglia-Mari G, Giglia-Mari G, Clarkson SG, Vermeulen W, Schärer OD.; ''Coordination of dual incision and repair synthesis in human nucleotide excision repair.''; PubMed Europe PMC Scholia
- Camenisch U, Träutlein D, Clement FC, Fei J, Leitenstorfer A, Ferrando-May E, Naegeli H.; ''Two-stage dynamic DNA quality check by xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
- de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, Hoeijmakers JH.; ''DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.''; PubMed Europe PMC Scholia
- Takedachi A, Saijo M, Tanaka K.; ''DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA.''; PubMed Europe PMC Scholia
- Fitch ME, Nakajima S, Yasui A, Ford JM.; ''In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.''; PubMed Europe PMC Scholia
- Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, Hanaoka F.; ''UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.''; PubMed Europe PMC Scholia
- Coin F, Oksenych V, Egly JM.; ''Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair.''; PubMed Europe PMC Scholia
- Oh KS, Imoto K, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH.; ''Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells.''; PubMed Europe PMC Scholia
- Kuraoka I, Ito S, Wada T, Hayashida M, Lee L, Saijo M, Nakatsu Y, Matsumoto M, Matsunaga T, Handa H, Qin J, Nakatani Y, Tanaka K.; ''Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair.''; PubMed Europe PMC Scholia
- van Cuijk L, van Belle GJ, van Belle GJ, Turkyilmaz Y, Poulsen SL, Janssens RC, Theil AF, Sabatella M, Lans H, Mailand N, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair.''; PubMed Europe PMC Scholia
- Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMed Europe PMC Scholia
- Morris DP, Michelotti GA, Schwinn DA.; ''Evidence that phosphorylation of the RNA polymerase II carboxyl-terminal repeats is similar in yeast and humans.''; PubMed Europe PMC Scholia
- Lindahl T, Wood RD.; ''Quality control by DNA repair.''; PubMed Europe PMC Scholia
- Araújo SJ, Wood RD.; ''Protein complexes in nucleotide excision repair.''; PubMed Europe PMC Scholia
History
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External references
DataNodes
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Annotated Interactions
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Source | Target | Type | Database reference | Comment |
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DDB1 | Arrow | REACT_1311 (Reactome) | ||
DDB1 | REACT_1492 (Reactome) | |||
DDB2 | Arrow | REACT_1311 (Reactome) | ||
DDB2 | REACT_1492 (Reactome) | |||
DNA Polymerase delta tetramer | Arrow | REACT_1196 (Reactome) | ||
DNA Polymerase delta tetramer | Arrow | REACT_465 (Reactome) | ||
DNA Polymerase delta tetramer | REACT_1196 (Reactome) | |||
DNA Polymerase delta tetramer | REACT_465 (Reactome) | |||
DNA Polymerase delta tetramer | mim-catalysis | REACT_1196 (Reactome) | ||
DNA Polymerase delta tetramer | mim-catalysis | REACT_465 (Reactome) | ||
DNA polymerase epsilon | Arrow | REACT_353 (Reactome) | ||
DNA polymerase epsilon | Arrow | REACT_677 (Reactome) | ||
DNA polymerase epsilon | REACT_353 (Reactome) | |||
DNA polymerase epsilon | REACT_677 (Reactome) | |||
DNA polymerase epsilon | mim-catalysis | REACT_353 (Reactome) | ||
DNA polymerase epsilon | mim-catalysis | REACT_677 (Reactome) | ||
ERCC1 XPF complex | Arrow | REACT_1311 (Reactome) | ||
ERCC1 XPF complex | REACT_1584 (Reactome) | |||
ERCC1 XPF complex | REACT_2163 (Reactome) | |||
ERCC1 | REACT_1438 (Reactome) | |||
ERCC4 | REACT_1438 (Reactome) | |||
ERCC5 | Arrow | REACT_1311 (Reactome) | ||
ERCC5 | REACT_1492 (Reactome) | |||
ERCC5 | REACT_1584 (Reactome) | |||
ERCC6 | REACT_1584 (Reactome) | |||
ERCC8 | REACT_1584 (Reactome) | |||
Incision complex with 3'-incised damaged DNA | mim-catalysis | REACT_1311 (Reactome) | ||
LIG1 | Arrow | REACT_2181 (Reactome) | ||
LIG1 | Arrow | REACT_527 (Reactome) | ||
LIG1 | REACT_2181 (Reactome) | |||
LIG1 | REACT_527 (Reactome) | |||
LIG1 | mim-catalysis | REACT_2181 (Reactome) | ||
LIG1 | mim-catalysis | REACT_527 (Reactome) | ||
PCNA homotrimer | Arrow | REACT_1196 (Reactome) | ||
PCNA homotrimer | Arrow | REACT_353 (Reactome) | ||
PCNA homotrimer | Arrow | REACT_465 (Reactome) | ||
PCNA homotrimer | Arrow | REACT_677 (Reactome) | ||
PCNA homotrimer | REACT_1196 (Reactome) | |||
PCNA homotrimer | REACT_353 (Reactome) | |||
PCNA homotrimer | REACT_465 (Reactome) | |||
PCNA homotrimer | REACT_677 (Reactome) | |||
RAD23B | REACT_1984 (Reactome) | |||
REACT_1033 (Reactome) | Two DNA helicases XPG and XPD, which are part of TFIIH, unwind DNA duplex around this lesion to form an open bubble structure that exposes the damaged site. | |||
REACT_1124 (Reactome) | The cleavage of the damaged strand of DNA 3' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The incision is carried out by XPG. | |||
REACT_1196 (Reactome) | At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA Polymerase delta tetramer', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA Polymerase delta tetramer', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'. | |||
REACT_1274 (Reactome) | At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present. This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'. | |||
REACT_1284 (Reactome) | At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'Stalled Pol II complex with damaged DNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present. This reaction takes place in the 'nucleus'. | |||
REACT_1311 (Reactome) | The cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The incision is carried out by ERCC1-XPF complex. | |||
REACT_1438 (Reactome) | At the beginning of this reaction, 1 molecule of 'ERCC1, DNA excision repair protein', and 1 molecule of 'XPF protein' are present. At the end of this reaction, 1 molecule of 'ERCC1:XPF complex' is present. This reaction takes place in the 'nucleus'. | |||
REACT_1453 (Reactome) | An active Pol II complex consisting mainly of the Pol II holoenzyme transcribes the damaged DNA template. | |||
REACT_1492 (Reactome) | Transcription factor II H (TFIIH) and XPG are added to the damaged site on the DNA to form a pre-incision complex along with lesioned DNA template. | |||
REACT_1584 (Reactome) | A proper assembly of repair complex may require displacement of Pol II from the damage site exposing a significant length of the corresponding template DNA with the lesions. Speculations on the mode of this displacement of Pol II are available from experimental evidences: a. CSB mediated dissociation of Pol II b. degradation of Pol II c. CSB mediated remodeling of damaged DNA-RNA PII interface etc. The TC-repair complex now consists of damaged DNA template: nascent mRNA hybrid. The damage site needs to be exposed to subsequent endonuclease activities. | |||
REACT_1947 (Reactome) | At the site of damage, the Pol II complex is arrested resulting in reduced levels of transcription. Several models have been proposed to explain the mechanism of this transcriptional downregulation. These include a. hyperphosphorylation of Pol II resulting in aborted entry to new pre-initiation complexes b. sequestration of TATA-binding proteins (TBP) c. enhanced use of TFIIH complexes for repair purposes precluding their use in transcription. | |||
REACT_1984 (Reactome) | XPC is mutated in individuals with xeroderma pigmentosum from genetic Complementation Group C (XP-C). It forms a tight heterodimeric complex with human Rad 23B homolog, HR23B and is thought to bind to the damaged site with lesion first triggering subsequent reactions | |||
REACT_1987 (Reactome) | Disruption of normal Watson-Crick base pairing and altered chemistry in the damaged strand involving bases may act as signals of damage that are recognized by XPC:HR23B complex. | |||
REACT_2163 (Reactome) | ERCC1-XPF complex with 5’ endonuclease activity binds to this pre-incision complex around the bubble structure to form an active incision complex. | |||
REACT_2181 (Reactome) | DNA Ligase 1 ligates the newly synthesized fragment to the gap in the template DNA. | |||
REACT_353 (Reactome) | At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA polymerase epsilon' are present. This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'. | |||
REACT_465 (Reactome) | At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA Polymerase delta tetramer' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA Polymerase delta tetramer' are present. This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'. | |||
REACT_527 (Reactome) | At the beginning of this reaction, 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA ligase I ', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'repaired DNA template:nascent mRNA hybrid', and 1 molecule of 'DNA ligase I ' are present. This reaction takes place in the 'nucleus' and is mediated by the 'DNA ligase activity' of 'DNA ligase I '. | |||
REACT_551 (Reactome) | At the beginning of this reaction, 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'repaired DNA template:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Active Pol II complex with repaired DNA template:mRNA hybrid' is present. This reaction takes place in the 'nucleus'. | |||
REACT_677 (Reactome) | At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'. | |||
REACT_811 (Reactome) | At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'excised DNA fragment with lesion', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'. | |||
RFC Heteropentamer | Arrow | REACT_1196 (Reactome) | ||
RFC Heteropentamer | Arrow | REACT_353 (Reactome) | ||
RFC Heteropentamer | Arrow | REACT_465 (Reactome) | ||
RFC Heteropentamer | Arrow | REACT_677 (Reactome) | ||
RFC Heteropentamer | REACT_1196 (Reactome) | |||
RFC Heteropentamer | REACT_353 (Reactome) | |||
RFC Heteropentamer | REACT_465 (Reactome) | |||
RFC Heteropentamer | REACT_677 (Reactome) | |||
RNA Polymerase II holoenzyme complex | REACT_1453 (Reactome) | |||
RPA heterotrimer | Arrow | REACT_1196 (Reactome) | ||
RPA heterotrimer | Arrow | REACT_1311 (Reactome) | ||
RPA heterotrimer | Arrow | REACT_353 (Reactome) | ||
RPA heterotrimer | Arrow | REACT_465 (Reactome) | ||
RPA heterotrimer | Arrow | REACT_677 (Reactome) | ||
RPA heterotrimer | REACT_1196 (Reactome) | |||
RPA heterotrimer | REACT_1492 (Reactome) | |||
RPA heterotrimer | REACT_353 (Reactome) | |||
RPA heterotrimer | REACT_465 (Reactome) | |||
RPA heterotrimer | REACT_677 (Reactome) | |||
Repaired double-stranded DNA | Arrow | REACT_2181 (Reactome) | ||
Stalled Pol II complex with damaged DNA hybrid | Arrow | REACT_1584 (Reactome) | ||
Stalled Pol II complex with damaged DNA hybrid | REACT_1284 (Reactome) | |||
Stalled Pol II complex with damaged DNA hybrid | REACT_1584 (Reactome) | |||
Stalled Pol II in TC-NER | Arrow | REACT_1284 (Reactome) | ||
Stalled Pol II in TC-NER | REACT_551 (Reactome) | |||
TCEA1 | REACT_1584 (Reactome) | |||
TFIIH | Arrow | REACT_1311 (Reactome) | ||
TFIIH | REACT_1492 (Reactome) | |||
TFIIH | REACT_1584 (Reactome) | |||
Transcription-coupled | Arrow | REACT_1274 (Reactome) | ||
Transcription-coupled | Arrow | REACT_1284 (Reactome) | ||
Transcription-coupled | Arrow | REACT_1584 (Reactome) | ||
Transcription-coupled | Arrow | REACT_811 (Reactome) | ||
Transcription-coupled | REACT_1274 (Reactome) | |||
Transcription-coupled | REACT_1284 (Reactome) | |||
Transcription-coupled | REACT_811 (Reactome) | |||
Transcription-coupled | mim-catalysis | REACT_1274 (Reactome) | ||
Transcription-coupled | mim-catalysis | REACT_811 (Reactome) | ||
XAB2 | REACT_1584 (Reactome) | |||
XPA | Arrow | REACT_1311 (Reactome) | ||
XPA | REACT_1492 (Reactome) | |||
XPC
HR23B damaged DNA complex | REACT_1492 (Reactome) | |||
XPC HR23B complex | Arrow | REACT_1311 (Reactome) | ||
XPC HR23B complex | REACT_1987 (Reactome) | |||
XPC | REACT_1984 (Reactome) | |||
dNTP | REACT_1196 (Reactome) | |||
dNTP | REACT_353 (Reactome) | |||
dNTP | REACT_465 (Reactome) | |||
dNTP | REACT_677 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid with 3' incision | Arrow | REACT_1274 (Reactome) | ||
damaged DNA substrate nascent mRNA hybrid with 3' incision | REACT_811 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid with dual incisions | Arrow | REACT_1196 (Reactome) | ||
damaged DNA substrate nascent mRNA hybrid with dual incisions | Arrow | REACT_677 (Reactome) | ||
damaged DNA substrate nascent mRNA hybrid with dual incisions | Arrow | REACT_811 (Reactome) | ||
damaged DNA substrate nascent mRNA hybrid with dual incisions | REACT_1196 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid with dual incisions | REACT_527 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid with dual incisions | REACT_677 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid | Arrow | REACT_1284 (Reactome) | ||
damaged DNA substrate nascent mRNA hybrid | REACT_1274 (Reactome) | |||
damaged DNA substrate nascent mRNA hybrid | REACT_1453 (Reactome) | |||
damaged DNA substrate | REACT_1987 (Reactome) | |||
excised DNA fragment with lesion | Arrow | REACT_1311 (Reactome) | ||
excised DNA fragment with lesion | Arrow | REACT_811 (Reactome) | ||
incised DNA without lesion | Arrow | REACT_1311 (Reactome) | ||
incised DNA without lesion | Arrow | REACT_353 (Reactome) | ||
incised DNA without lesion | Arrow | REACT_465 (Reactome) | ||
incised DNA without lesion | REACT_2181 (Reactome) | |||
incised DNA without lesion | REACT_353 (Reactome) | |||
incised DNA without lesion | REACT_465 (Reactome) | |||
incision complex for GG-NER | mim-catalysis | REACT_1124 (Reactome) | ||
newly synthesized DNA fragment | Arrow | REACT_1196 (Reactome) | ||
newly synthesized DNA fragment | Arrow | REACT_353 (Reactome) | ||
newly synthesized DNA fragment | Arrow | REACT_465 (Reactome) | ||
newly synthesized DNA fragment | Arrow | REACT_677 (Reactome) | ||
newly synthesized DNA fragment | REACT_2181 (Reactome) | |||
newly synthesized DNA fragment | REACT_527 (Reactome) | |||
pre-incision complex in GG-NER | mim-catalysis | REACT_1033 (Reactome) | ||
pre-incision complex with open DNA bubble | REACT_2163 (Reactome) | |||
repaired DNA template nascent mRNA hybrid | Arrow | REACT_527 (Reactome) | ||
repaired DNA template nascent mRNA hybrid | REACT_551 (Reactome) |