Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis
Abstract ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase...
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2025-01-01
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| author | Jing Wang Chunshuang Li Jinling Han Yaoyao Xue Xu Zheng Ruoxi Wang Zsolt Radak Yusaku Nakabeppu Istvan Boldogh Xueqing Ba |
| author_facet | Jing Wang Chunshuang Li Jinling Han Yaoyao Xue Xu Zheng Ruoxi Wang Zsolt Radak Yusaku Nakabeppu Istvan Boldogh Xueqing Ba |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Abstract ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome. The accumulation of genomic 8-oxoGua and the dysfunction of OGG1 is readily linked to mutagenesis, and subsequently aging-related diseases and tumorigenesis; however, the direct experimental evidence has long been lacking. Recently, a series of studies have shown that guanine oxidation in the genome has a conservative bias, with the tendency to occur in the regulatory regions, thus, 8-oxoGua is not only a lesion to be repaired, but also an epigenetic modification. In this regard, OGG1 is a specific reader of this base modification. Substrate recognition and/or excision by OGG1 can cause DNA conformation changes, affect chromatin modifications, thereby modulating the transcription of genes involved in a variety of cellular processes, including inflammation, cell proliferation, differentiation, and apoptosis. Thus, in addition to the potential mutagenicity, 8-oxoGua may contribute to tumor development and progression through the altered gene expression stemming from its epigenetic effects. |
| format | Article |
| id | doaj-art-ff474f0fb1d64a7e883373aeba9f5c98 |
| institution | Kabale University |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Biomedical Science |
| spelling | doaj-art-ff474f0fb1d64a7e883373aeba9f5c982025-01-05T12:42:31ZengBMCJournal of Biomedical Science1423-01272025-01-0132111310.1186/s12929-024-01093-8Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesisJing Wang0Chunshuang Li1Jinling Han2Yaoyao Xue3Xu Zheng4Ruoxi Wang5Zsolt Radak6Yusaku Nakabeppu7Istvan Boldogh8Xueqing Ba9Department of Respiratory Medicine, China-Japan Union Hospital of Jilin UniversityKey Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal UniversityKey Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal UniversityKey Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal UniversityKey Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal UniversityCollege of Life Sciences, Shandong Normal UniversityResearch Institute of Sport Science, University of Physical EducationDivision of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Microbiology and Immunology, University of Texas Medical Branch at GalvestonKey Laboratory of Molecular Epigenetics of Ministry of Education, College of Life Sciences, Northeast Normal UniversityAbstract ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome. The accumulation of genomic 8-oxoGua and the dysfunction of OGG1 is readily linked to mutagenesis, and subsequently aging-related diseases and tumorigenesis; however, the direct experimental evidence has long been lacking. Recently, a series of studies have shown that guanine oxidation in the genome has a conservative bias, with the tendency to occur in the regulatory regions, thus, 8-oxoGua is not only a lesion to be repaired, but also an epigenetic modification. In this regard, OGG1 is a specific reader of this base modification. Substrate recognition and/or excision by OGG1 can cause DNA conformation changes, affect chromatin modifications, thereby modulating the transcription of genes involved in a variety of cellular processes, including inflammation, cell proliferation, differentiation, and apoptosis. Thus, in addition to the potential mutagenicity, 8-oxoGua may contribute to tumor development and progression through the altered gene expression stemming from its epigenetic effects.https://doi.org/10.1186/s12929-024-01093-88-oxoguanineOGG1Epigenetic regulationGene expressionTumorigenesis |
| spellingShingle | Jing Wang Chunshuang Li Jinling Han Yaoyao Xue Xu Zheng Ruoxi Wang Zsolt Radak Yusaku Nakabeppu Istvan Boldogh Xueqing Ba Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis Journal of Biomedical Science 8-oxoguanine OGG1 Epigenetic regulation Gene expression Tumorigenesis |
| title | Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis |
| title_full | Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis |
| title_fullStr | Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis |
| title_full_unstemmed | Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis |
| title_short | Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis |
| title_sort | reassessing the roles of oxidative dna base lesion 8 oxogua and repair enzyme ogg1 in tumorigenesis |
| topic | 8-oxoguanine OGG1 Epigenetic regulation Gene expression Tumorigenesis |
| url | https://doi.org/10.1186/s12929-024-01093-8 |
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