The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA
The interaction of chemical and physical agents with genetic material can lead to almost 80 different DNA damage formations. The targeted intentional DNA damage by radiotherapy or chemotherapy is a front-line anticancer therapy. An interstrand cross-link can result from ionization radiation or speci...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253118302853 |
| _version_ | 1818303094700638208 |
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| author | Boleslaw T. Karwowski |
| author_facet | Boleslaw T. Karwowski |
| author_sort | Boleslaw T. Karwowski |
| collection | DOAJ |
| description | The interaction of chemical and physical agents with genetic material can lead to almost 80 different DNA damage formations. The targeted intentional DNA damage by radiotherapy or chemotherapy is a front-line anticancer therapy. An interstrand cross-link can result from ionization radiation or specific chemical agents, such as trans-/cisplatin activity. Here, the influence of the adenine and thymidine (AT) interstrand linkage, the covalent bond between the adenine N6 and thymidine C5 methylene group, on the isolated base pair as well as double-stranded DNA (dsDNA) was taken into quantum mechanical/molecular mechanical (QM/MM) consideration at the m062x/6-31+G*:UFF level of theory in the aqueous phase. All the results presented in this article, for the first time, show that an AT-interstrand cross-link (ICL) changes the positive and negative charge migration process due to a higher activation energy forced by the cross-link’s presence. However, the final radical cation destination in cross-linked DNA is left in the same place as in a native double-stranded-deoxyoligonucleotide. Additionally, the direction of the radical anion transfer was found to be opposite to that of native dsDNA. Therefore, it can be postulated that the appearance of the AT-ICL does not disturb the hole migration in the double helix, with subsequent effective changes in the electron migration process. Keywords: DNA damage, AT interstrand cross-link, charge transfer, DFT, dsDNA structure |
| first_indexed | 2024-12-13T05:49:20Z |
| format | Article |
| id | doaj.art-0c9c26cedeae4cb58936dd266e506f48 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-13T05:49:20Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-0c9c26cedeae4cb58936dd266e506f482022-12-21T23:57:36ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-12-0113665685The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNABoleslaw T. Karwowski0DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland; Corresponding author: Boleslaw T. Karwowski, DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland.The interaction of chemical and physical agents with genetic material can lead to almost 80 different DNA damage formations. The targeted intentional DNA damage by radiotherapy or chemotherapy is a front-line anticancer therapy. An interstrand cross-link can result from ionization radiation or specific chemical agents, such as trans-/cisplatin activity. Here, the influence of the adenine and thymidine (AT) interstrand linkage, the covalent bond between the adenine N6 and thymidine C5 methylene group, on the isolated base pair as well as double-stranded DNA (dsDNA) was taken into quantum mechanical/molecular mechanical (QM/MM) consideration at the m062x/6-31+G*:UFF level of theory in the aqueous phase. All the results presented in this article, for the first time, show that an AT-interstrand cross-link (ICL) changes the positive and negative charge migration process due to a higher activation energy forced by the cross-link’s presence. However, the final radical cation destination in cross-linked DNA is left in the same place as in a native double-stranded-deoxyoligonucleotide. Additionally, the direction of the radical anion transfer was found to be opposite to that of native dsDNA. Therefore, it can be postulated that the appearance of the AT-ICL does not disturb the hole migration in the double helix, with subsequent effective changes in the electron migration process. Keywords: DNA damage, AT interstrand cross-link, charge transfer, DFT, dsDNA structurehttp://www.sciencedirect.com/science/article/pii/S2162253118302853 |
| spellingShingle | Boleslaw T. Karwowski The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA Molecular Therapy: Nucleic Acids |
| title | The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA |
| title_full | The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA |
| title_fullStr | The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA |
| title_full_unstemmed | The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA |
| title_short | The AT Interstrand Cross-Link: Structure, Electronic Properties, and Influence on Charge Transfer in dsDNA |
| title_sort | at interstrand cross link structure electronic properties and influence on charge transfer in dsdna |
| url | http://www.sciencedirect.com/science/article/pii/S2162253118302853 |
| work_keys_str_mv | AT boleslawtkarwowski theatinterstrandcrosslinkstructureelectronicpropertiesandinfluenceonchargetransferindsdna AT boleslawtkarwowski atinterstrandcrosslinkstructureelectronicpropertiesandinfluenceonchargetransferindsdna |