Oxoguanine glycosylase

OGG1
Gene ontology
Molecular function	DNA binding microtubule binding hydrolase activity, acting on glycosyl bonds oxidized purine DNA binding catalytic activity protein binding oxidized purine nucleobase lesion DNA N-glycosylase activity lyase activity endonuclease activity 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity hydrolase activity damaged DNA binding DNA N-glycosylase activity class I DNA-(apurinic or apyrimidinic site) endonuclease activity
Cellular component	mitochondrion nuclear matrix nucleus nuclear speck nucleoplasm protein-containing complex
Biological process	depurination nucleotide-excision repair response to estradiol regulation of transcription, DNA-templated response to light stimulus human ageing negative regulation of apoptotic process cellular response to cadmium ion response to oxidative stress depyrimidination acute inflammatory response response to radiation response to folic acid metabolism response to ethanol nucleotide-excision repair, DNA incision negative regulation of double-strand break repair via single-strand annealing base-excision repair cellular response to DNA damage stimulus DNA repair base-excision repair, AP site formation telomere maintenance via telomerase
Sources:Amigo / QuickGO

Ensembl				ENSG00000114026	ENSMUSG00000030271
UniProt	O15527	O08760
RefSeq (mRNA)	NM_002542 NM_016819 NM_016820 NM_016821 NM_016826 NM_016827 NM_016828 NM_016829 NM_001354648 NM_001354649 NM_001354650 NM_001354651 NM_001354652	NM_010957
RefSeq (protein)	NP_002533 NP_058212 NP_058213 NP_058214 NP_058434 NP_058436 NP_058437 NP_058438 NP_001341577 NP_001341578 NP_001341579 NP_001341580 NP_001341581 NP_058436.1 NP_058434.1	NP_035087
Location (UCSC)	Chr 3: 9.75 – 9.79 Mb	Chr 6: 113.3 – 113.31 Mb
PubMed search	[3]	[4]

Wikidata

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8-oxoguanine DNA glycosylase, N-terminal domain
SCOP2		1ebm / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

8-Oxoguanine glycosylase, also known as OGG1, is a

.

Function

OGG1 is the primary enzyme responsible for the excision of

Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan,

]

Increased oxidant stress temporarily inactivates OGG1, which recruits transcription factors such as

OGG1 deficiency and increased 8-oxo-dG in mice

Mice without a functional OGG1 gene have about a 5-fold increased level of 8-oxo-dG in their livers compared to mice with wild-type OGG1.

. The irradiated OGG1 knock-out mice went on to develop more than twice the incidence of skin tumors compared to irradiated wild-type mice, and the rate of malignancy within the tumors was higher in the OGG1 knock-out mice (73%) than in the wild-type mice (50%).

As reviewed by Valavanidis et al.,^[14] increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found during carcinogenesis.

In the figure showing examples of mouse colonic epithelium, the colonic epithelium from a mouse on a normal diet was found to have a low level of 8-oxo-dG in its colonic crypts (panel A). However, a mouse likely undergoing colonic tumorigenesis (due to deoxycholate added to its diet^[12]) was found to have a high level of 8-oxo-dG in its colonic epithelium (panel B). Deoxycholate increases intracellular production of reactive oxygen resulting in increased oxidative stress,^[15]>^[16] and this can lead to tumorigenesis and carcinogenesis.

Epigenetic control

In a breast cancer study, the methylation level of the OGG1 promoter was found to be negatively correlated with expression level of OGG1 messenger RNA.^[17] This means that hypermethylation was associated with low expression of OGG1 and hypomethylation was correlated with over-expression of OGG1. Thus, OGG1 expression is under epigenetic control. Breast cancers with methylation levels of the OGG1 promoter that were more than two standard deviations either above or below the normal were each associated with reduced patient survival.^[17]

In cancers

OGG1 is the primary enzyme responsible for the excision of 8-oxo-dG. Even when OGG1 expression is normal, the presence of 8-oxo-dG is mutagenic, since OGG1 is not 100% effective. Yasui et al.^[18] examined the fate of 8-oxo-dG when this oxidized derivative of deoxyguanosine was inserted into a specific gene in 800 cells in culture. After replication of the cells, 8-oxo-dG was restored to G in 86% of the clones, probably reflecting accurate OGG1 base excision repair or translesion synthesis without mutation. G:C to T:A transversions occurred in 5.9% of the clones, single base deletions in 2.1% and G:C to C:G transversions in 1.2%. Together, these mutations were the most common, totalling 9.2% of the 14% of mutations generated at the site of the 8-oxo-dG insertion. Among the other mutations in the 800 clones analyzed, there were also 3 larger deletions, of sizes 6, 33 and 135 base pairs. Thus 8-oxo-dG can directly cause mutations, some of which may contribute to carcinogenesis.

If OGG1 expression is reduced in cells, increased mutagenesis, and therefore increased carcinogenesis, would be expected. The table below lists some cancers associated with reduced expression of OGG1.

Table 1. OGG1 expression in sporadic cancers

Cancer	Expression	Form of OGG1	8-oxo-dG	Evaluation method	Ref.
Head and neck cancer	Under-expression	OGG1-2a	-	messenger RNA	[19]
Adenocarcinoma of gastric cardia	Under-expression	cytoplasmic	increased	immunohistochemistry	[20]
Astrocytoma	Under-expression	total cell OGG1	-	messenger RNA	[21]
Esophageal cancer	48% Under-expression	nuclear	increased	immunohistochemistry	[22]
-	40% Under-expression	cytoplasm	increased	immunohistochemistry	[22]

OGG1 or OGG activity in blood, and cancer

OGG1 methylation levels in blood cells were measured in a prospective study of 582 US military veterans, median age 72, and followed for 13 years. High OGG1 methylation at a particular promoter region was associated with increased risk for any cancer, and in particular for risk of prostate cancer.^[23]

Enzymatic activity excising

An important effect on cancer is expected to derive from the drastic enhancement of gene expression for certain immunity genes, which OGG1 regulates.[26]

Interactions

Oxoguanine glycosylase has been shown to

Pathology

• OGG1 may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.^[29]

References

Further reading

• Boiteux S, Radicella JP (May 2000). "The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis". Archives of Biochemistry and Biophysics. 377 (1): 1–8.
  PMID 10775435
  .
• Park J, Chen L, Tockman MS, Elahi A, Lazarus P (February 2004). "The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk". Pharmacogenetics. 14 (2): 103–109.
  PMID 15077011
  .
• Hung RJ, Hall J, Brennan P, Boffetta P (November 2005). "Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review". American Journal of Epidemiology. 162 (10): 925–942.
  PMID 16221808
  .
• Mirbahai L, Kershaw RM, Green RM, Hayden RE, Meldrum RA, Hodges NJ (February 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.
  PMID 20042377
  .
• Wang R, Hao W, Pan L, Boldogh I, Ba X (October 2018). "The roles of base excision repair enzyme OGG1 in gene expression". Cellular and Molecular Life Sciences. 75 (20): 3741–3750.
  PMID 30043138
  .
• Vlahopoulos S, Adamaki M, Khoury N, Zoumpourlis V, Boldogh I (2018). "Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer". Pharmacology & Therapeutics. 194: 59–72.
  PMID 30240635
  .

External links

• oxoguanine+glycosylase+1,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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