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.
Wang QE, Zhu Q, Wani G, Chen J, Wani AA.; ''UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2.''; PubMedEurope PMCScholia
Robu M, Shah RG, Petitclerc N, Brind'Amour J, Kandan-Kulangara F, Shah GM.; ''Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.''; PubMedEurope PMCScholia
Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH.; ''Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo.''; PubMedEurope PMCScholia
Lee KB, Wang D, Lippard SJ, Sharp PA.; ''Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro.''; PubMedEurope PMCScholia
Shiyanov P, Nag A, Raychaudhuri P.; ''Cullin 4A associates with the UV-damaged DNA-binding protein DDB.''; PubMedEurope PMCScholia
Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D.; ''Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.''; PubMedEurope PMCScholia
Winkler GS, Sugasawa K, Eker AP, de Laat WL, Hoeijmakers JH.; ''Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.''; PubMedEurope PMCScholia
Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y.; ''Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.''; PubMedEurope PMCScholia
Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, Coin F, Egly JM, Tanaka K.; ''XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients.''; PubMedEurope PMCScholia
Birger Y, West KL, Postnikov YV, Lim JH, Furusawa T, Wagner JP, Laufer CS, Kraemer KH, Bustin M.; ''Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin.''; PubMedEurope PMCScholia
Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM.; ''Nucleotide excision repair driven by the dissociation of CAK from TFIIH.''; PubMedEurope PMCScholia
Brueckner F, Hennecke U, Carell T, Cramer P.; ''CPD damage recognition by transcribing RNA polymerase II.''; PubMedEurope PMCScholia
Ziani S, Nagy Z, Alekseev S, Soutoglou E, Egly JM, Coin F.; ''Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin.''; PubMedEurope PMCScholia
Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly JM.; ''Molecular structure of human TFIIH.''; PubMedEurope PMCScholia
Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL.; ''UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.''; PubMedEurope PMCScholia
Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH, Pommier Y.; ''Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.''; PubMedEurope PMCScholia
Orelli B, McClendon TB, Tsodikov OV, Ellenberger T, Niedernhofer LJ, Schärer OD.; ''The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways.''; PubMedEurope PMCScholia
Selby CP, Sancar A.; ''Cockayne syndrome group B protein enhances elongation by RNA polymerase II.''; PubMedEurope PMCScholia
Kuper J, Wolski SC, Michels G, Kisker C.; ''Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation.''; PubMedEurope PMCScholia
Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F.; ''The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA.''; PubMedEurope PMCScholia
Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S.; ''Characterization of DNA recognition by the human UV-damaged DNA-binding protein.''; PubMedEurope PMCScholia
Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH.; ''A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein.''; PubMedEurope PMCScholia
Camenisch U, Dip R, Schumacher SB, Schuler B, Naegeli H.; ''Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.''; PubMedEurope PMCScholia
Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, Hensbergen P, Deelder A, de Groot A, Matsumoto S, Sugasawa K, Thoma N, Vermeulen W, Vrieling H, Mullenders L.; ''PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.''; PubMedEurope PMCScholia
Anindya R, Mari PO, Kristensen U, Kool H, Giglia-Mari G, Giglia-Mari G, Mullenders LH, Fousteri M, Vermeulen W, Egly JM, Svejstrup JQ.; ''A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair.''; PubMedEurope PMCScholia
Overmeer RM, Moser J, Volker M, Kool H, Tomkinson AE, van Zeeland AA, Mullenders LH, Fousteri M.; ''Replication protein A safeguards genome integrity by controlling NER incision events.''; PubMedEurope PMCScholia
Dunand-Sauthier I, Hohl M, Thorel F, Jaquier-Gubler P, Clarkson SG, Schärer OD.; ''The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity.''; PubMedEurope PMCScholia
King BS, Cooper KL, Liu KJ, Hudson LG.; ''Poly(ADP-ribose) contributes to an association between poly(ADP-ribose) polymerase-1 and xeroderma pigmentosum complementation group A in nucleotide excision repair.''; PubMedEurope PMCScholia
Park CH, Bessho T, Matsunaga T, Sancar A.; ''Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.''; PubMedEurope PMCScholia
Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K.; ''XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription.''; PubMedEurope PMCScholia
Dinant C, Ampatziadis-Michailidis G, Lans H, Tresini M, Lagarou A, Grosbart M, Theil AF, van Cappellen WA, Kimura H, Bartek J, Fousteri M, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage.''; PubMedEurope PMCScholia
Conaway RC, Conaway JW.; ''The INO80 chromatin remodeling complex in transcription, replication and repair.''; PubMedEurope PMCScholia
Mackinnon-Roy C, Stubbert LJ, McKay BC.; ''RNA interference against transcription elongation factor SII does not support its role in transcription-coupled nucleotide excision repair.''; PubMedEurope PMCScholia
Riedl T, Hanaoka F, Egly JM.; ''The comings and goings of nucleotide excision repair factors on damaged DNA.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Christmann M, Tomicic MT, Roos WP, Kaina B.; ''Mechanisms of human DNA repair: an update.''; PubMedEurope PMCScholia
Min JH, Pavletich NP.; ''Recognition of DNA damage by the Rad4 nucleotide excision repair protein.''; PubMedEurope PMCScholia
Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, Hoeijmakers JH, Demmers JA, Fousteri M, Vermeulen W, Marteijn JA.; ''UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair.''; PubMedEurope PMCScholia
Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH.; ''Understanding nucleotide excision repair and its roles in cancer and ageing.''; PubMedEurope PMCScholia
Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F.; ''Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J, Wani AA.; ''DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation.''; PubMedEurope PMCScholia
Balajee AS, May A, Dianova I, Bohr VA.; ''Efficient PCNA complex formation is dependent upon both transcription coupled repair and genome overall repair.''; PubMedEurope PMCScholia
Scrima A, Konícková R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thomä NH.; ''Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.''; PubMedEurope PMCScholia
Hanawalt PC, Spivak G.; ''Transcription-coupled DNA repair: two decades of progress and surprises.''; PubMedEurope PMCScholia
Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L.; ''INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway.''; PubMedEurope PMCScholia
Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T.; ''Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.''; PubMedEurope PMCScholia
Fei J, Chen J.; ''KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR).''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Schärer OD, Wagner G, Ellenberger T.; ''Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA.''; PubMedEurope PMCScholia
Sarker AH, Tsutakawa SE, Kostek S, Ng C, Shin DS, Peris M, Campeau E, Tainer JA, Nogales E, Cooper PK.; ''Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome.''; PubMedEurope PMCScholia
Rossignol M, Kolb-Cheynel I, Egly JM.; ''Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH.''; PubMedEurope PMCScholia
Mathieu N, Kaczmarek N, Naegeli H.; ''Strand- and site-specific DNA lesion demarcation by the xeroderma pigmentosum group D helicase.''; PubMedEurope PMCScholia
Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K.; ''Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair.''; PubMedEurope PMCScholia
Poulsen SL, Hansen RK, Wagner SA, van Cuijk L, van Belle GJ, Streicher W, Wikström M, Choudhary C, Houtsmuller AB, Marteijn JA, Bekker-Jensen S, Mailand N.; ''RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response.''; PubMedEurope PMCScholia
Fang L, Wang X, Yamoah K, Chen PL, Pan ZQ, Huang L.; ''Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry.''; PubMedEurope PMCScholia
Jawhari A, Lainé JP, Dubaele S, Lamour V, Poterszman A, Coin F, Moras D, Egly JM.; ''p52 Mediates XPB function within the transcription/repair factor TFIIH.''; PubMedEurope PMCScholia
Epshtein V, Kamarthapu V, McGary K, Svetlov V, Ueberheide B, Proshkin S, Mironov A, Nudler E.; ''UvrD facilitates DNA repair by pulling RNA polymerase backwards.''; PubMedEurope PMCScholia
Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders LH, Fousteri MI.; ''Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Oksenych V, Bernardes de Jesus B, Zhovmer A, Egly JM, Coin F.; ''Molecular insights into the recruitment of TFIIH to sites of DNA damage.''; PubMedEurope PMCScholia
Ahel D, Horejsí Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ.; ''Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.''; PubMedEurope PMCScholia
Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM.; ''Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH.''; PubMedEurope PMCScholia
Reardon JT, Ge H, Gibbs E, Sancar A, Hurwitz J, Pan ZQ.; ''Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.''; PubMedEurope PMCScholia
Groisman R, Groisman R, Kuraoka I, Chevallier O, Gaye N, Magnaldo T, Tanaka K, Kisselev AF, Harel-Bellan A, Nakatani Y.; ''CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.''; PubMedEurope PMCScholia
Vermeulen W, Fousteri M.; ''Mammalian transcription-coupled excision repair.''; PubMedEurope PMCScholia
Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, Nakazawa Y, Niimi A, Miki Y, Jaspers NG, Mullenders LH, Yamashita S, Fousteri MI, Lehmann AR.; ''Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Groisman R, Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y.; ''The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Zotter A, Luijsterburg MS, Warmerdam DO, Ibrahim S, Nigg A, van Cappellen WA, Hoeijmakers JH, van Driel R, Vermeulen W, Houtsmuller AB.; ''Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Wakasugi M, Kasashima H, Fukase Y, Imura M, Imai R, Yamada S, Cleaver JE, Matsunaga T.; ''Physical and functional interaction between DDB and XPA in nucleotide excision repair.''; PubMedEurope PMCScholia
He Z, Henricksen LA, Wold MS, Ingles CJ.; ''RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Hofmann RM, Pickart CM.; ''Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.''; PubMedEurope PMCScholia
Sarkar S, Kiely R, McHugh PJ.; ''The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Fitch ME, Nakajima S, Yasui A, Ford JM.; ''In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMedEurope PMCScholia
Morris DP, Michelotti GA, Schwinn DA.; ''Evidence that phosphorylation of the RNA polymerase II carboxyl-terminal repeats is similar in yeast and humans.''; PubMedEurope PMCScholia
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.
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.
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'.
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'.
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.
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.
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.
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.
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.
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
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.
ERCC1-XPF complex with 5’ endonuclease activity binds to this pre-incision complex around the bubble structure to form an active incision complex.
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'.
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'.
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 '.
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.
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'.
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'.
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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HR23B
damaged DNA complexAnnotated Interactions
This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.
This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.
This reaction takes place in the 'nucleus'.
This reaction takes place in the 'nucleus'.
The TC-repair complex now consists of damaged DNA template: nascent mRNA hybrid. The damage site needs to be exposed to subsequent endonuclease activities.
This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'.
This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.
This reaction takes place in the 'nucleus' and is mediated by the 'DNA ligase activity' of 'DNA ligase I '.
This reaction takes place in the 'nucleus'.
This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'.
This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.
HR23B
damaged DNA complex