BioPAX pathway converted from "Defective OGG1 Substrate Processing" in the Reactome database.
Defective OGG1 Substrate Processing
Defective OGG1 Substrate Processing
大多数OGG1突变体检测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.
Authored: Orlic-Milacic, Marija, 2019-07-30
Reviewed: Vlahopoulos, Spiros, 2019-10-02
Reviewed: Boldogh, Istvan, 2019-10-08
Edited: Orlic-Milacic, Marija, 2019-10-10
OGG1 S326C is oxidized
OGG1 S326C is oxidized
OGG1 S326C是一个频繁的遗传多态性,前sent in more than 20% of people of European and Asian descent (Janssen et al. 2001, Moritz et al. 2014). On its own, substitution of serine with cysteine at position 326 does not affect the catalytic activity of OGG1 (Dherin et al. 1999, Janssen et al. 2001, Moritz et al. 2014). However, under oxidative stress, OGG1 S326C variant is more susceptible to oxidation or nitrosation than the wild type enzyme (Moritz et al. 2014), which diminishes catalytic activity and leads to accumulation of genomic 8-oxoguanine (8oxoG) (Yamane et al. 2004, Moritz et al. 2014) under conditions of oxidative stress (Kershaw and Hodges 2012). This may be due to decreased specificity of OGG1 S326C for 8oxoG and FapyG (Dherin et al. 1999).
The frequency of OGG1 S326C allele is increased in NSCLC patients and the level of 8-oxodG is higher in lung tissue and leukocytes of these patients (Janik et al. 2011). OGG1 S326C variant is associated with an increased breast cancer risk (Ali et al. 2015).
Authored: Orlic-Milacic, Marija, 2019-07-30
Reviewed: Vlahopoulos, Spiros, 2019-10-02
Reviewed: Boldogh, Istvan, 2019-10-08
Edited: Orlic-Milacic, Marija, 2019-10-10
Reactome DB_ID: 9658769
1
nucleoplasm
GO
0005654
UniProt:O15527 OGG1
OGG1
MUTM
OGH1
OGG1
MMH
FUNCTION DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the type-1 OGG1 family.
Reactome
//www.joaskin.com
Homo sapiens
NCBI Taxonomy
9606
UniProt
O15527
l-serine 326 replaced with L-cysteine
326
EQUAL
l-serine removal [MOD:01646]
Chain Coordinates
1
EQUAL
345
EQUAL
Reactome DB_ID: 3785707
1
reactive oxygen species [ChEBI:26523]
reactive oxygen species
ChEBI
26523
Reactome DB_ID: 9658815
1
l-serine 326 replaced with L-cysteine
326
EQUAL
l-cysteine sulfenic acid at 326
326
EQUAL
l-cysteine sulfenic acid
1
EQUAL
345
EQUAL
Reactome Database ID Release 77
9658813
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9658813
Reactome
R-HSA-9658813
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9658813.1
21376741
Pubmed
2011
8-Oxoguanine incision activity is impaired in lung tissues of NSCLC patients with the polymorphism of OGG1 and XRCC1 genes
Janik, Justyna
Swoboda, Maja
Janowska, Beata
Cieśla, Jarosław M
Gackowski, Daniel
Kowalewski, Janusz
Olinski, Ryszard
Tudek, Barbara
Speina, Elżbieta
Mutat. Res. 709:21-31
26089588
Pubmed
2015
OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data
Ali, Kashif
Mahjabeen, Ishrat
Sabir, Maimoona
Mehmood, Humera
Kayani, Mahmood Akhtar
Dis. Markers 2015:690878
24632493
Pubmed
2014
hOGG1-Cys326 variant cells are hypersensitive to DNA repair inhibition by nitric oxide
Moritz, Eva
Pauly, Karin
Bravard, Anne
Hall, Janet
Radicella, J Pablo
Epe, Bernd
Carcinogenesis 35:1426-33
Defective OGG1 mutants do not excise 8-oxoguanine
Defective OGG1 mutants do not excise 8-oxoguanine
OGG1 missense mutants OGG1 R46Q (Audebert, Chevillard et al. 2000; Audebert, Radicella et al. 2000), reported in clear cell renal carcinoma, and OGG1 R154H (Audebert, Radicella et al. 2000), reported in gastric cancer cell line MKN4 (Bruner et al. 2000), show a diminished 8-oxoguanine (8oxoG)-directed DNA glycosylase activity, with the function of OGG1 R154H being more severely impaired. The first functional study of OGG1 R154H reported catalytic activity similar to the wild type OGG1, but promiscuous substrate binding, which could result in a mutator phenotype (Bruner et al. 2000).
OGG1 R131Q mutant, reported in lung cancer, shows the loss of 8oxoG-directed glycolytic activity (Chevillard et al. 1998), which, based on structural studies, is predicted to be the consequence of misfolding of the active site (Bruner et al. 2000, Anderson and Dagget 2009). Distortion of the active site was also found to be the cause of impaired function of OGG1 R46Q and OGG1 R154H.
OGG1 missense mutant, OGG1 R229Q, reported in the acute myeloid leukemia-derived cell line KG-1, shows a loss of 8oxoG-directed DNA glycosylase activity (Hyun et al. 2000, Hyun et al. 2002), which is due to thermolability of the OGG1 R229Q mutant (Hill and Evans 2007).
OGG1 frameshift mutant, OGG1 P266fs139*, reported in Alzheimer's disease, exhibits loss of glycosylase activity and is unable to excise 8oxoG from damaged DNA (Mao et al. 2007).
It is uncertain whether substrate binding is affected in OGG1 R46Q, OGG1 R229Q and OGG1 P266fs139*. Excision of FapyG from dsDNA by OGG1 R46Q, OGG1 R131Q, OGG1 R229Q and OGG1 P266fs139* has not been tested.
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 is a frequent genetic polymorphism in people of European and Asian descent. OGG1 S326C variant is susceptible to oxidation, leading to diminished catalytic activity and accumulation of 8oxoG (Yamane et al. 2004, Moritz et al. 2014) under conditions of oxidative stress (Kershaw and Hodges 2012). This may be due to decreased specificity of OGG1 S326C for 8oxoG (Dherin et al. 1999).
Lysine 249 (K249) of OGG1 is directly involved in the nucleophilic attack of the N-glycosidic bond while aspartate 268 (D268) of OGG1 primes K249 for the nucleophilic attack. Both K249 and D268 are critical for the excision of 8oxoG lesions from damaged DNA. By directed mutagenesis, OGG1 K249Q (Nash et al. 1997), OGG1 D268A (Bjoras et al. 2002) and OGG1 D268N (Bjoras et al. 2002, Norman et al. 2003, Sebera et al. 2017) mutants were shown to be non-functional in 8oxoG cleavage. Naturally occurring variant alleles of OGG1 that produce OGG1 K249Q, OGG1 D268A and OGG1 D268N have been reported in human populations (ClinGene Allele Registry - Pawliczek et al. 2018) but have so far not been associated with a specific disease.
Authored: Orlic-Milacic, Marija, 2019-07-30
Reviewed: Vlahopoulos, Spiros, 2019-10-02
Reviewed: Boldogh, Istvan, 2019-10-08
Edited: Orlic-Milacic, Marija, 2019-10-10
Reactome DB_ID: 9656301
1
OGG1 mutants:(8oxoG:Cyt)-dsDNA [nucleoplasm]
OGG1 mutants:(8oxoG:Cyt)-dsDNA
Reactome DB_ID: 110184
1
(8oxoG:Cyt)-dsDNA [nucleoplasm]
(8oxoG:Cyt)-dsDNA
Double-strand DNA containing an 8-oxo guanine opposite to a cytosine
Converted from EntitySet in Reactome
Reactome DB_ID: 9656300
1
OGG1 mutants (8oxoG hydrolysis) [nucleoplasm]
Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity
OGG1 D268N [nucleoplasm]
OGG1 R46Q [nucleoplasm]
OGG1 D268A [nucleoplasm]
OGG1 R131Q [nucleoplasm]
OGG1 P266fs139* [nucleoplasm]
OGG1 K249Q [nucleoplasm]
OGG1 R229Q [nucleoplasm]
SOH-C326-OGG1 S326C [nucleoplasm]
OGG1 R154H [nucleoplasm]
Reactome Database ID Release 77
9656301
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9656301
Reactome
R-HSA-9656301
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9656301.1
Reactome Database ID Release 77
9656250
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9656250
Reactome
R-HSA-9656250
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9656250.1
17651912
Pubmed
2007
A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents
Hill, Jeff W
Evans, Michele K
癌症检测。Prev 31:237-43。
12578369
Pubmed
2003
Structural and biochemical exploration of a critical amino acid in human 8-oxoguanine glycosylase
Norman, Derek P G
Chung, SJ
Verdine, GL
Biochemistry 42:1564-72
22451681
Pubmed
2012
Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1
Kershaw, Rachael M
Hodges, Nikolas J
Mutagenesis 27:501-10
11902834
Pubmed
2002
Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase
Bjørås, Magnar
Seeberg, Erling
luna, Luisa
Pearl, Laurence H
Barrett, Tracey E
J. Mol. Biol. 317:171-7
10908322
Pubmed
2000
Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein
Audebert, M
Radicella, J P
Dizdaroglu, M
Nucleic Acids Res. 28:2672-8
11002420
Pubmed
2000
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, J W
Choi, J Y
Zeng, H H
lee, Y S
Kim, H S
Yoon, S H
Chung, M H
Oncogene 19:4476-9
9331411
Pubmed
1997
The critical active-site amine of the human 8-oxoguanine DNA glycosylase, hOgg1: direct identification, ablation and chemical reconstitution
Nash, H M
lu, R
lane, WS
Verdine, G L
Chem. Biol. 4:693-702
17426120
Pubmed
2007
Identification and characterization of OGG1 mutations in patients with Alzheimer's disease
Mao, Guogen
锅,小雨
Zhu, Bei-Bei
Zhang, Yanbin
Yuan, Fenghua
Huang, Jian
lovell, Mark A
lee, Maxwell P
Markesbery, William R
li, Guo-Min
Gu, Liya
Nucleic Acids Res. 35:2759-66
19537786
Pubmed
2009
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, Peter C
Daggett, Valerie
J. Am. Chem. Soc. 131:9506-15
9662341
Pubmed
1998
Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours
Chevillard, S
Radicella, J P
levalois, C
lebeau, J
Poupon, M F
Oudard, S
Dutrillaux, B
Boiteux, S
Oncogene 16:3083-6
10706276
Pubmed
2000
Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA
Bruner, S D
Norman, D P
Verdine, G L
Nature 403:859-66
11827746
Pubmed
2002
Radiation sensitivity depends on OGG1 activity status in human leukemia cell lines
Hyun, Jin-Won
Cheon, Gi-Jeong
Kim, Hyun-Sook
lee, Yun-Sil
Choi, Eun-Young
Yoon, Byung-Hak
Kim, Jeong-Soon
Chung, Myung-Hee
Free Radic. Biol. Med. 32:212-20
28334993
Pubmed
2017
The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine
Šebera, Jakub
Hattori, Yoshikazu
Sato, Daichi
Reha, David
Nencka, Radim
Kohno, Takashi
Kojima, Chojiro
Tanaka, Yoshiyuki
Sychrovský, Vladimír
Nucleic Acids Res. 45:5231-5242
30311374
Pubmed
2018
ClinGen Allele Registry links information about genetic variants
Pawliczek, Piotr
Patel Ronak Y
Ashmore, Lillian R
Jackson, Andrew R
Bizon, Chris
Nelson, Tristan
Powell, Bradford
Freimuth, RR
Strande, Natasha
Shah, Neethu
Paithankar, Sameer
Wright, Matt W
Dwight, Selina
Zhen, Jimmy
landrum, Melissa
McGarvey, Peter
Babb, Larry
Plon, Sharon E
Milosavljevic, Aleksandar
Clinical Genome (ClinGen) Resource, -
Hum. Mutat. 39:1690-1701
10987279
Pubmed
2000
Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney
Audebert, M
Chevillard, S
levalois, C
Gyapay, G
Vieillefond, A
Klijanienko, J
Vielh, P
El Naggar, A K
Oudard, S
Boiteux, S
Radicella, J P
Cancer Res. 60:4740-4
10497264
Pubmed
1999
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
Dherin, C
Radicella, J P
Dizdaroglu, M
Boiteux, S
Nucleic Acids Res. 27:4001-7
Defective OGG1 mutants do not excise FapyG
Defective OGG1 mutants do not excise FapyG
OGG1 R46Q mutant, reported in renal carcinoma, and OGG1 R154H mutant, reported in stomach cancer cell line MKN4 (Bruner et al. 2000), show decreased excision of FapyG from dsDNA (Audebert, Radicella et al. 2000), with the function of OGG1 R154H being more severely impaired. It is uncertain whether binding to FapyG in dsDNA substrate is affected in OGG1 R46Q and OGG1 R154H.
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 based on its similarity with OGG1 R46L.
OGG1 S326C is a frequent genetic polymorphism in people of European and Asian descent. OGG1 S326C variant is susceptible to oxidative modifications, leading to diminished catalytic activity (Yamane et al. 2004, Moritz et al. 2014) under conditions of oxidative stress (Kershaw and Hodges 2012). This may be due to decreased specificity of OGG1 S326C for FapyG (Dherin et al. 1999).
Authored: Orlic-Milacic, Marija, 2019-07-30
Reviewed: Vlahopoulos, Spiros, 2019-10-02
Reviewed: Boldogh, Istvan, 2019-10-08
Edited: Orlic-Milacic, Marija, 2019-10-10
Reactome DB_ID: 9657134
1
OGG1 mutants:FapyG-dsDNA [nucleoplasm]
OGG1 mutants:FapyG-dsDNA
OGG1 R46Q,OGG1 R154H,SOH-C326-OGG1 S326C,(OGG1 R46L):FapyG-dsDNA
OGG1 R46Q,OGG1 R154H,SOH-C326-OGG1 S326C,(OGG1 R46L):formamidopyrimidine complex
Reactome DB_ID: 110182
1
FapyG-dsDNA [nucleoplasm]
FapyG-dsDNA
Double-strand DNA containing 2,6-diamino-4-hydroxy-5-formamido-pyrimidine
Converted from EntitySet in Reactome
Reactome DB_ID: 9657137
1
OGG1 mutants (FapyG hydrolysis) [nucleoplasm]
Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity
OGG1 R46Q [nucleoplasm]
SOH-C326-OGG1 S326C [nucleoplasm]
OGG1 R154H [nucleoplasm]
Reactome Database ID Release 77
9657134
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9657134
Reactome
R-HSA-9657134
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9657134.1
Reactome Database ID Release 77
9656252
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9656252
Reactome
R-HSA-9656252
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9656252.1
15073047
Pubmed
2004
Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo
Yamane, Arito
Kohno, Takashi
伊藤浩平表示
Sunaga, Noriaki
Aoki, Kazunori
Yoshimura, Kimio
Murakami, Hirokazu
Nojima, Yoshihisa
Yokota, Jun
Carcinogenesis 25:1689-94
Reactome Database ID Release 77
9656256
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9656256
Reactome
R-HSA-9656256
1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9656256.1