Summary: 8-oxoguanine DNA glycosylase, N-terminal domain
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Oxoguanine glycosylase Edit Wikipedia article
|8-oxoguanine DNA glycosylase|
PDB rendering based on 1ebm.
|Symbols||; HMMH; HOGG1; MUTM; OGH1|
|RNA expression pattern|
|8-oxoguanine DNA glycosylase, N-terminal domain|
structure of catalytically inactive q315a human 8-oxoguanine glycosylase complexed to 8-oxoguanine dna
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.
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. 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.
Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan, and Ogg1 knockout mice have a more possibility to develop cancer ,whereas Mth1 gene disruption concomitantly suppresses lung cancer development in Ogg1-/- mice.[dubious ] 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. 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.
- "Entrez Gene: OGG1 8-oxoguanine DNA glycosylase".
- Bjoras 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, R. L.; 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; Swe-Brca; Arver, B; Rantala, J; Loman, N; Ehrencrona, H; Olopade, O. I.; Beattie, M. S.; Domchek, S. M.; Nathanson, K; Rebbeck, T. R. et al. (2014). "DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers". PLoS Genetics 10 (4): e1004256. doi:10.1371/journal.pgen.1004256. PMID 24698998.
- 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 et al. (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 (2006). "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 9 (2): 144–152. doi:10.1016/j.dnarep.2009.11.009. PMID 20042377.
- oxoguanine glycosylase 1, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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8-oxoguanine DNA glycosylase, N-terminal domain Provide feedback
The presence of 8-oxoguanine residues in DNA can give rise to G-C to T-A transversion mutations. This enzyme is found in archaeal, bacterial and eukaryotic species, and is specifically responsible for the process which leads to the removal of 8-oxoguanine residues. It has DNA glycosylase activity ( EC:220.127.116.11) and DNA lyase activity ( EC:18.104.22.168) . The region featured in this family is the N-terminal domain, which is organised into a single copy of a TBP-like fold. The domain contributes residues to the 8-oxoguanine binding pocket .
Bjoras M, Seeberg E, Luna L, Pearl LH, Barrett TE; , J Mol Biol 2002;317:171-177.: Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase. PUBMED:11902834 EPMC:11902834
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR012904
The presence of 8-oxoguanine residues in DNA can give rise to G-C to T-A transversion mutations. This enzyme is found in archaeal, bacterial and eukaryotic species, and is specifically responsible for the process which leads to the removal of 8-oxoguanine residues. It has DNA glycosylase activity (EC) and DNA lyase activity (EC) [PUBMED:10706276]. The region featured in this family is the N-terminal domain, which is organised into a single copy of a TBP-like fold. The domain contributes residues to the 8-oxoguanine binding pocket [PUBMED:11902834].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||damaged DNA binding (GO:0003684)|
|oxidized purine base lesion DNA N-glycosylase activity (GO:0008534)|
|Biological process||nucleotide-excision repair (GO:0006289)|
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TBP is a transcription factor whose DNA binding fold is composed of a curved antiparallel beta-sheet . This fold is also found in the N terminal region of DNA repair glycosylases. The N terminal domain of DNA glycosylase has only a single copy of the fold, whereas TBP contains a duplication of this fold [2-3].
The clan contains the following 3 members:AlkA_N OGG_N TBP
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Key: available, not generated, — not available.
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|Seed source:||Pfam-B_29151 (release 14.0)|
|Number in seed:||95|
|Number in full:||767|
|Average length of the domain:||113.40 aa|
|Average identity of full alignment:||26 %|
|Average coverage of the sequence by the domain:||34.56 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||7|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the OGG_N domain has been found. There are 31 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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