Defective OGG1 Substrate Processing

Stable Identifier
Homo sapiens
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The majority of OGG1 mutants have been tested for their ability to excise 8-oxoguanine (8oxoG) from damaged DNA, while a small number of mutants have been tested for the ability to remove FapyG from DNA.
The following OGG1 mutants show at least a partial loss of their ability to remove 8oxoG:
OGG1 R46Q (Audebert, Chevillard et al. 2000; Audebert, Radicella et al. 2000);
OGG1 R154H (Audebert, Radicella et al. 2000, Bruner et al. 2000);
OGG1 R131Q (Chevillard et al. 1998, Bruner et al. 2000, Anderson and Dagget 2009);
OGG1 R229Q (Hyun et al. 2000, Hyun et al. 2002, Hill and Evans 2007);
OGG1 P266fs139* (Mao et al. 2007).
OGG1 R46L and OGG1 R131G have not been functionally studied but have been reported in cancer and predicted to be pathogenic. They are annotated as candidate disease variants based on their similarity with OGG1 R46Q and OGG1 R131Q, respectively.
OGG1 S326C, a frequent variant in European and Asian populations, is susceptible to oxidation, which diminishes catalytic activity under conditions of oxidative stress (Dherin et al. 1999, Yamane et al. 2004, Kershaw and Hodges 2012, Moritz et al. 2014).
The following OGG1 mutants show at least a partial loss of their ability to remove FapyG:
OGG1 R46Q (Audebert, Radicella et al. 2000);
OGG1 R154H (Audebert, Radicella et al. 2000).
OGG1 R46L has not been functionally studied but has been reported in cancer and predicted to be pathogenic. It is annotated as a candidate disease variant for FapyG excision, based on its similarity with OGG1 R46Q.
Literature References
PubMed ID Title Journal Year
19537786 The R46Q, R131Q and R154H polymorphs of human DNA glycosylase/beta-lyase hOgg1 severely distort the active site and DNA recognition site but do not cause unfolding

Anderson, PC, Daggett, V

J. Am. Chem. Soc. 2009
11002420 Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1

Hyun, JW, Chung, MH, Lee, YS, Kim, HS, Zeng, HH, Choi, JY, Yoon, SH

Oncogene 2000
10987279 Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney

Chevillard, S, Oudard, S, El Naggar, AK, Klijanienko, J, Radicella, JP, Vielh, P, Levalois, C, Boiteux, S, Audebert, M, Vieillefond, A, Gyapay, G

Cancer Res. 2000
17426120 Identification and characterization of OGG1 mutations in patients with Alzheimer's disease

Huang, J, Zhang, Y, Mao, G, Pan, X, Li, GM, Markesbery, WR, Yuan, F, Lee, MP, Lovell, MA, Gu, L, Zhu, BB

Nucleic Acids Res. 2007
24632493 hOGG1-Cys326 variant cells are hypersensitive to DNA repair inhibition by nitric oxide

Radicella, JP, Hall, J, Pauly, K, Epe, B, Bravard, A, Moritz, E

Carcinogenesis 2014
10908322 Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein

Radicella, JP, Audebert, M, Dizdaroglu, M

Nucleic Acids Res. 2000
17651912 A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents

Hill, JW, Evans, MK

Cancer Detect. Prev. 2007
22451681 Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1

Hodges, NJ, Kershaw, RM

Mutagenesis 2012
10497264 Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations

Radicella, JP, Boiteux, S, Dizdaroglu, M, Dherin, C

Nucleic Acids Res. 1999
9662341 Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours

Chevillard, S, Oudard, S, Poupon, MF, Radicella, JP, Levalois, C, Dutrillaux, B, Boiteux, S, Lebeau, J

Oncogene 1998
10706276 Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

Bruner, SD, Verdine, GL, Norman, DP

Nature 2000
11827746 Radiation sensitivity depends on OGG1 activity status in human leukemia cell lines

Yoon, BH, Kim, HS, Chung, MH, Kim, JS, Choi, EY, Hyun, JW, Lee, YS, Cheon, GJ

Free Radic. Biol. Med. 2002
Name Identifier Synonyms
Alzheimer's disease DOID:10652 AD, Alzheimers dementia, Alzheimer disease
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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