Oxoguanine glycosylase
| 8-oxoguanine DNA glycosylase, N-terminal domain | |||||||||
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 structure of catalytically inactive q315a human 8-oxoguanine glycosylase complexed to 8-oxoguanine dna | |||||||||
| Identifiers | |||||||||
| Symbol | OGG_N | ||||||||
| Pfam | PF07934 | ||||||||
| Pfam clan | CL0407 | ||||||||
| InterPro | IPR012904 | ||||||||
| SCOP | 1ebm | ||||||||
| SUPERFAMILY | 1ebm | ||||||||
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8-Oxoguanine glycosylase also known as OGG1 is a DNA glycosylase enzyme that, in humans, is encoded by the OGG1 gene. It is involved in base excision repair. It is found in bacterial, archaeal and eukaryotic species.
Function
OGG1 is the primary enzyme responsible for the excision of 8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species (ROS). OGG1 is a bifunctional glycosylase, as it is able to both cleave the glycosidic bond of the mutagenic lesion and cause a strand break in the DNA backbone. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants have the N-terminal region in common. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. In eukaryotes, the N-terminus of this gene contains a mitochondrial targeting signal, essential for mitochondrial localization.[1] A conserved N-terminal domain contributes residues to the 8-oxoguanine binding pocket. This domain is organised into a single copy of a TBP-like fold.[2]
Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan,[3] and Ogg1 knockout mice have a higher probability to develop cancer, whereas Mth1 gene disruption concomitantly suppresses lung cancer development in Ogg1-/- mice. Interestingly, mice lacking Ogg1 have been shown to be prone to increased body weight and obesity, as well as high-fat diet induced insulin resistance.[4] There is some controversy as to whether deletion of Ogg1 actually leads to increased 8-oxo-dG levels: the HPLC-EC assay suggests up to 6 fold higher levels of 8-oxo-dG in nuclear DNA and 20-fold higher in mitochondrial DNA whereas the fappy-glycosylase assay indicates no change.
Interactions
Oxoguanine glycosylase has been shown to interact with XRCC1[5] and PKC alpha.[6]
Pathology
References
- ↑ "Entrez Gene: OGG1 8-oxoguanine DNA glycosylase".
- ↑ Bjørås M, Seeberg E, Luna L, Pearl LH, Barrett TE (March 2002). "Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase". J. Mol. Biol. 317 (2): 171–7. doi:10.1006/jmbi.2002.5400. PMID 11902834.
- ↑ Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B, Seeberg E, Lindahl T, Barnes DE (November 1999). "Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage". Proc. Natl. Acad. Sci. U.S.A. 96 (23): 13300–5. doi:10.1073/pnas.96.23.13300. PMC 23942. PMID 10557315.
- ↑ Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS (December 2012). "8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction". PLoS ONE 7 (12): e51697. doi:10.1371/journal.pone.0051697. PMC 3524114. PMID 23284747.
- ↑ Marsin S, Vidal AE, Sossou M, Ménissier-de Murcia J, Le Page F, Boiteux S, de Murcia G, Radicella JP (November 2003). "Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1". J. Biol. Chem. 278 (45): 44068–74. doi:10.1074/jbc.M306160200. PMID 12933815.
- ↑ Dantzer F, Luna L, Bjørås M, Seeberg E (June 2002). "Human OGG1 undergoes serine phosphorylation and associates with the nuclear matrix and mitotic chromatin in vivo". Nucleic Acids Res. 30 (11): 2349–57. doi:10.1093/nar/30.11.2349. PMC 117190. PMID 12034821.
- ↑ Osorio A, Milne RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I, de la Hoya M, Duran M, Díez O, Ramón Y, Cajal T, Konstantopoulou I, Martínez-Bouzas C, Andrés Conejero R, Soucy P, McGuffog L, Barrowdale D, Lee A, Arver B, Rantala J, Loman N, Ehrencrona H, Olopade OI, Beattie MS, Domchek SM, Nathanson K, Rebbeck TR, Arun BK, Karlan BY, Walsh C, Lester J, John EM, Whittemore AS, Daly MB, Southey M, Hopper J, Terry MB, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Hansen TV, Jønson L, Ejlertsen B, Gerdes AM, Infante M, Herráez B, Moreno LT, Weitzel JN, Herzog J, Weeman K, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Bonanni B, Mariette F, Volorio S, Viel A, Varesco L, Papi L, Ottini L, Tibiletti MG, Radice P, Yannoukakos D, Garber J, Ellis S, Frost D, Platte R, Fineberg E, Evans G, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Eccles D, Cook J, Hodgson S, Brewer C, Tischkowitz M, Douglas F, Porteous M, Side L, Walker L, Morrison P, Donaldson A, Kennedy J, Foo C, Godwin AK, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, Meindl A, Ditsch N, Arnold N, Plendl HJ, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Gehrig A, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Damiola F, Poppe B, Claes K, Piedmonte M, Tucker K, Backes F, Rodríguez G, Brewster W, Wakeley K, Rutherford T, Caldés T, Nevanlinna H, Aittomäki K, Rookus MA, van Os TA, van der Kolk L, de Lange JL, Meijers-Heijboer HE, van der Hout AH, van Asperen CJ, Gómez Garcia EB, Hoogerbrugge N, Collée JM, van Deurzen CH, van der Luijt RB, Devilee P, Olah E, Lázaro C, Teulé A, Menéndez M, Jakubowska A, Cybulski C, Gronwald J, Lubinski J, Durda K, Jaworska-Bieniek K, Johannsson OT, Maugard C, Montagna M, Tognazzo S, Teixeira MR, Healey S, Investigators K, Olswold C, Guidugli L, Lindor N, Slager S, Szabo CI, Vijai J, Robson M, Kauff N, Zhang L, Rau-Murthy R, Fink-Retter A, Singer CF, Rappaport C, Geschwantler Kaulich D, Pfeiler G, Tea MK, Berger A, Phelan CM, Greene MH, Mai PL, Lejbkowicz F, Andrulis I, Mulligan AM, Glendon G, Toland AE, Bojesen A, Pedersen IS, Sunde L, Thomassen M, Kruse TA, Jensen UB, Friedman E, Laitman Y, Shimon SP, Simard J, Easton DF, Offit K, Couch FJ, Chenevix-Trench G, Antoniou AC, Benitez J (2014). "DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers". PLoS Genet. 10 (4): e1004256. doi:10.1371/journal.pgen.1004256. PMC 3974638. PMID 24698998.
Further reading
- Boiteux S, Radicella JP (2000). "The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis". Arch. Biochem. Biophys. 377 (1): 1–8. doi:10.1006/abbi.2000.1773. PMID 10775435.
- Park J, Chen L, Tockman MS, Elahi A, Lazarus P (2004). "The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk". Pharmacogenetics 14 (2): 103–9. doi:10.1097/00008571-200402000-00004. PMID 15077011.
- Hung RJ, Hall J, Brennan P, Boffetta P (2005). "Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review". Am. J. Epidemiol. 162 (10): 925–42. doi:10.1093/aje/kwi318. PMID 16221808.
- Mirbahai L, Kershaw RM, Green RM, Hayden RE, Meldrum RA, Hodges NJ (2010). "Use of a molecular beacon to track the activity of base excision repair protein OGG1 in live cells". DNA Repair (Amst.) 9 (2): 144–52. doi:10.1016/j.dnarep.2009.11.009. PMID 20042377.
External links
- oxoguanine glycosylase 1, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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This article incorporates text from the public domain Pfam and InterPro IPR012904