Oxoguanine glycosylase

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8-oxoguanine DNA glycosylase

PDB rendering based on 1ebm.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols OGG1 ; HMMH; HOGG1; MUTM; OGH1
External IDs OMIM601982 MGI1097693 HomoloGene1909 GeneCards: OGG1 Gene
EC number 4.2.99.18
RNA expression pattern
PBB GE OGG1 205301 s at tn.png
PBB GE OGG1 205760 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4968 18294
Ensembl ENSG00000114026 ENSMUSG00000030271
UniProt O15527 O08760
RefSeq (mRNA) NM_002542 NM_010957
RefSeq (protein) NP_002533 NP_035087
Location (UCSC) Chr 3:
9.79 – 9.83 Mb
Chr 6:
113.33 – 113.34 Mb
PubMed search [1] [2]
8-oxoguanine DNA glycosylase, N-terminal domain
PDB 2noh EBI.jpg
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

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[edit]

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 konckout mice have a more possibility to develop cancer ,whereas Mth1 gene disruption concomitantly suppresses lung cancer development in Ogg1-/- mice.[citation needed][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.[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.[citation needed]

Interactions[edit]

Oxoguanine glycosylase has been shown to interact with XRCC1[5] and PKC alpha.[6]

Pathology[edit]

  • OGG1 may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.[7]

References[edit]

  1. ^ "Entrez Gene: OGG1 8-oxoguanine DNA glycosylase". 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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.  edit

Further reading[edit]

  • 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[edit]


This article incorporates text from the public domain Pfam and InterPro IPR012904