Oxoguanine glycosylase

8-oxoguanine DNA glycosylase
PDB rendering based on 1ebm.
Available structures PDB 1EBM, 1FN7, 1HU0, 1KO9, 1LWV, 1LWW, 1LWY, 1M3H, 1M3Q, 1N39, 1N3A, 1N3C, 1YQK, 1YQL, 1YQM, 1YQR, 2I5W, 2NOB, 2NOE, 2NOF, 2NOH, 2NOI, 2NOL, 2NOZ, 3IH7, 3KTU
Identifiers
Symbols	OGG1; HMMH; HOGG1; MUTM; OGH1
External IDs	OMIM: 601982 MGI: 1097693 HomoloGene: 1909 GeneCards: OGG1 Gene
EC number	4.2.99.18
Gene Ontology Molecular function • damaged DNA binding • endonuclease activity • protein binding • oxidized purine base lesion DNA N-glycosylase activity • hydrolase activity, acting on glycosyl bonds • lyase activity Cellular component • nucleus • nucleoplasm • nucleoplasm • nucleoplasm • nucleolus • cytoplasm • mitochondrion • nuclear matrix • nuclear speck Biological process • DNA repair • base-excision repair • base-excision repair, AP site formation • nucleotide-excision repair • regulation of transcription, DNA-dependent • response to oxidative stress • response to radiation • regulation of protein import into nucleus, translocation • depurination • depurination Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4968	18294
Ensembl	ENSG00000114026	ENSMUSG00000030271
UniProt	O15527	Q3UIL3
RefSeq (mRNA)	NM_002542.5	NM_010957.4
RefSeq (protein)	NP_002533.1	NP_035087.3
Location (UCSC)	Chr 3: 9.79 – 9.83 Mb	Chr 6: 113.28 – 113.29 Mb
PubMed search	[1]	[2]

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.

Function

OGG1 is the primary enzyme responsible for the excision of 7,8-dihydro-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. The N-terminus of this gene contains a mitochondrial targeting signal, essential for mitochondrial localization.^[1]

Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan,^[2] and despite some early reports, do not show increased mutagenesis or cancer incidence.^{[citation needed][dubious – discuss]} 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.^{[citation needed]}

Interactions

Oxoguanine glycosylase has been shown to interact with XRCC1^[3] and PKC alpha.^[4]

References

1. ^ "Entrez Gene: OGG1 8-oxoguanine DNA glycosylase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4968. 
2. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23942. 
3. ^ Marsin, Stéphanie; Vidal Antonio E, Sossou Marguerite, Ménissier-de Murcia Josiane, Le Page Florence, Boiteux Serge, de Murcia Gilbert, Radicella J Pablo (Nov. 2003). "Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1". J. Biol. Chem. (United States) 278 (45): 44068–74. doi:10.1074/jbc.M306160200. ISSN 0021-9258. PMID 12933815. 
4. ^ Dantzer, Françoise; Luna Luisa, Bjørås Magnar, Seeberg Erling (Jun. 2002). "Human OGG1 undergoes serine phosphorylation and associates with the nuclear matrix and mitotic chromatin in vivo". Nucleic Acids Res. (England) 30 (11): 2349–57. doi:10.1093/nar/30.11.2349. PMC 117190. PMID 12034821. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=117190. 

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 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. 

External links

• MeSH oxoguanine+glycosylase+1,+human