Genetically Encoded Photosensitizer Targeted to Methylated DNA
Genetically encoded photosensitizers are widely used in fundamental research and translational medicine due to their ability to generate reactive oxygen species (ROS) after photosensitizing. Previously, it was shown in mice that red dimeric fluorescent protein KillerRed is a potential photosensitize...
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MDPI AG
2022-11-01
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| Series: | Medical Sciences Forum |
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| Online Access: | https://www.mdpi.com/2673-9992/14/1/21 |
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| author | Anastasiia Gorshkova Dmitry Gorbachev Mariia Moshareva Lidiya Putlyaeva Konstantin Lukyanov |
| author_facet | Anastasiia Gorshkova Dmitry Gorbachev Mariia Moshareva Lidiya Putlyaeva Konstantin Lukyanov |
| author_sort | Anastasiia Gorshkova |
| collection | DOAJ |
| description | Genetically encoded photosensitizers are widely used in fundamental research and translational medicine due to their ability to generate reactive oxygen species (ROS) after photosensitizing. Previously, it was shown in mice that red dimeric fluorescent protein KillerRed is a potential photosensitizer that can be used for photodynamic therapy of cancer. In addition, it was demonstrated that HeLa cells expressing KillerRed fused to histone H2B cease proliferation upon illumination. A DNA repair protein, X-ray repair cross-complementing protein 1 (XRCC1), redistributed in the cell nuclei, indicating that the mechanism of phototoxic action of the construct involved DNA breaks generation. Here, we have constructed and tested a new genetically encoded photosensitizer molecule which introduces DNA breaks and activates the repair system in cancer-derived and embryonic cell lines more efficiently than previously described. The molecule consists of two parts: a SuperNova2 (monomeric mutant of KillerRed with enhanced phototoxicity) and methyl-CpG binding protein MECP2. The complex activates XRCC1 redistribution after illumination with lower power compared to the previously used construct. We suppose it can be explained by the tighter contact between photosensitizer and DNA. In addition, we hypothesize that the system should be error-prone for the expressed genes as it is targeted to the DNA which is silenced by methylation. Taking everything into consideration, the new genetically encoded construct has shown the improved ability to generate DNA breaks in the cancer cell lines. |
| first_indexed | 2024-03-11T06:06:29Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2673-9992 |
| language | English |
| last_indexed | 2024-03-11T06:06:29Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-bc9e71d92938466f97257f11253d8f4b2023-11-17T12:57:04ZengMDPI AGMedical Sciences Forum2673-99922022-11-011412110.3390/ECMC2022-13654Genetically Encoded Photosensitizer Targeted to Methylated DNAAnastasiia Gorshkova0Dmitry Gorbachev1Mariia Moshareva2Lidiya Putlyaeva3Konstantin Lukyanov4Skolkovo Institute of Science and Technology, 121205 Moscow, RussiaInstitute of Bioorganic Chemistry, 117997 Moscow, RussiaInstitute of Bioorganic Chemistry, 117997 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaGenetically encoded photosensitizers are widely used in fundamental research and translational medicine due to their ability to generate reactive oxygen species (ROS) after photosensitizing. Previously, it was shown in mice that red dimeric fluorescent protein KillerRed is a potential photosensitizer that can be used for photodynamic therapy of cancer. In addition, it was demonstrated that HeLa cells expressing KillerRed fused to histone H2B cease proliferation upon illumination. A DNA repair protein, X-ray repair cross-complementing protein 1 (XRCC1), redistributed in the cell nuclei, indicating that the mechanism of phototoxic action of the construct involved DNA breaks generation. Here, we have constructed and tested a new genetically encoded photosensitizer molecule which introduces DNA breaks and activates the repair system in cancer-derived and embryonic cell lines more efficiently than previously described. The molecule consists of two parts: a SuperNova2 (monomeric mutant of KillerRed with enhanced phototoxicity) and methyl-CpG binding protein MECP2. The complex activates XRCC1 redistribution after illumination with lower power compared to the previously used construct. We suppose it can be explained by the tighter contact between photosensitizer and DNA. In addition, we hypothesize that the system should be error-prone for the expressed genes as it is targeted to the DNA which is silenced by methylation. Taking everything into consideration, the new genetically encoded construct has shown the improved ability to generate DNA breaks in the cancer cell lines.https://www.mdpi.com/2673-9992/14/1/21genetically encoded photosensitizerKillerRed |
| spellingShingle | Anastasiia Gorshkova Dmitry Gorbachev Mariia Moshareva Lidiya Putlyaeva Konstantin Lukyanov Genetically Encoded Photosensitizer Targeted to Methylated DNA Medical Sciences Forum genetically encoded photosensitizer KillerRed |
| title | Genetically Encoded Photosensitizer Targeted to Methylated DNA |
| title_full | Genetically Encoded Photosensitizer Targeted to Methylated DNA |
| title_fullStr | Genetically Encoded Photosensitizer Targeted to Methylated DNA |
| title_full_unstemmed | Genetically Encoded Photosensitizer Targeted to Methylated DNA |
| title_short | Genetically Encoded Photosensitizer Targeted to Methylated DNA |
| title_sort | genetically encoded photosensitizer targeted to methylated dna |
| topic | genetically encoded photosensitizer KillerRed |
| url | https://www.mdpi.com/2673-9992/14/1/21 |
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