Oxoguanine glycosylase

From Wikipedia, the free encyclopedia
Jump to: navigation, search
8-oxoguanine DNA glycosylase
Protein OGG1 PDB 1ebm.png
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 knockout mice have a higher probability 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. ^ 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. 
  3. ^ Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B et al. (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 et al. (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 RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R et al. (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[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, 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[edit]


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