Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene
Abstract The chemistry of DNA and its repair selectivity control the influence of genomic oxidative stress on the development of serious disorders such as cancer and heart diseases. DNA is oxidized by endogenous reactive oxygen species (ROS) in vivo or in vitro as a result of high energy radiation,...
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2019-03-01
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| Series: | ChemistryOpen |
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| Online Access: | https://doi.org/10.1002/open.201800292 |
| _version_ | 1797771195344486400 |
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| author | Di Jiang Prof. James F. Rusling |
| author_facet | Di Jiang Prof. James F. Rusling |
| author_sort | Di Jiang |
| collection | DOAJ |
| description | Abstract The chemistry of DNA and its repair selectivity control the influence of genomic oxidative stress on the development of serious disorders such as cancer and heart diseases. DNA is oxidized by endogenous reactive oxygen species (ROS) in vivo or in vitro as a result of high energy radiation, non‐radiative metabolic processes, and other consequences of oxidative stress. Some oxidations of DNA and tumor suppressor gene p53 are thought to be mutagenic when not repaired. For example, site‐specific oxidations of p53 tumor suppressor gene may lead to cancer‐related mutations at the oxidation site codon. This review summarizes the research on the primary products of the most easily oxidized nucleobase guanine (G) when different oxidation methods are used. Guanine is by far the most oxidized DNA base. The primary initial oxidation product of guanine for most, but not all, pathways is 8‐oxoguanine (8‐oxoG). With an oxidation potential much lower than G, 8‐oxoG is readily susceptible to further oxidation, and the products often depend on the oxidants. Specific products may control the types of subsequent mutations, but mediated by gene repair success. Site‐specific oxidations of p53 tumor suppressor gene have been reported at known mutation hot spots, and the codon sites also depend on the type of oxidants. Modern methodologies using LC–MS/MS for codon specific detection and identification of oxidation sites are summarized. Future work aimed at understanding DNA oxidation in nucleosomes and interactions between DNA damage and repair is needed to provide a better picture of how cancer‐related mutations arise. |
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| institution | Directory Open Access Journal |
| issn | 2191-1363 |
| language | English |
| last_indexed | 2024-03-12T21:33:59Z |
| publishDate | 2019-03-01 |
| publisher | Wiley-VCH |
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| spelling | doaj.art-df963431dd414b29bc19eec461769ce12023-07-27T14:18:46ZengWiley-VCHChemistryOpen2191-13632019-03-018325226510.1002/open.201800292Oxidation Chemistry of DNA and p53 Tumor Suppressor GeneDi Jiang0Prof. James F. Rusling1Department of Chemistry University of Connecticut Storrs CT 06269 United StatesDepartment of Chemistry University of Connecticut Storrs CT 06269 United StatesAbstract The chemistry of DNA and its repair selectivity control the influence of genomic oxidative stress on the development of serious disorders such as cancer and heart diseases. DNA is oxidized by endogenous reactive oxygen species (ROS) in vivo or in vitro as a result of high energy radiation, non‐radiative metabolic processes, and other consequences of oxidative stress. Some oxidations of DNA and tumor suppressor gene p53 are thought to be mutagenic when not repaired. For example, site‐specific oxidations of p53 tumor suppressor gene may lead to cancer‐related mutations at the oxidation site codon. This review summarizes the research on the primary products of the most easily oxidized nucleobase guanine (G) when different oxidation methods are used. Guanine is by far the most oxidized DNA base. The primary initial oxidation product of guanine for most, but not all, pathways is 8‐oxoguanine (8‐oxoG). With an oxidation potential much lower than G, 8‐oxoG is readily susceptible to further oxidation, and the products often depend on the oxidants. Specific products may control the types of subsequent mutations, but mediated by gene repair success. Site‐specific oxidations of p53 tumor suppressor gene have been reported at known mutation hot spots, and the codon sites also depend on the type of oxidants. Modern methodologies using LC–MS/MS for codon specific detection and identification of oxidation sites are summarized. Future work aimed at understanding DNA oxidation in nucleosomes and interactions between DNA damage and repair is needed to provide a better picture of how cancer‐related mutations arise.https://doi.org/10.1002/open.201800292DNA mutationsDNA oxidationLC–MS/MSoxidative productsp53 tumor suppressor gene |
| spellingShingle | Di Jiang Prof. James F. Rusling Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene ChemistryOpen DNA mutations DNA oxidation LC–MS/MS oxidative products p53 tumor suppressor gene |
| title | Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene |
| title_full | Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene |
| title_fullStr | Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene |
| title_full_unstemmed | Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene |
| title_short | Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene |
| title_sort | oxidation chemistry of dna and p53 tumor suppressor gene |
| topic | DNA mutations DNA oxidation LC–MS/MS oxidative products p53 tumor suppressor gene |
| url | https://doi.org/10.1002/open.201800292 |
| work_keys_str_mv | AT dijiang oxidationchemistryofdnaandp53tumorsuppressorgene AT profjamesfrusling oxidationchemistryofdnaandp53tumorsuppressorgene |