Conservation of dark CPD photolyase function in blind cavefish
Abstract DNA damage is generated by various environmental stressors and so DNA repair systems must inevitably adapt to changing environments. Photolyases represent a highly conserved class of enzymes which repair UV-induced covalent crosslinks between adjacent pyrimidine bases (CPD and 6-4 photoprod...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62795-7 |
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| author | Hongxiang Li Carina Scheitle Giuseppe Di Mauro Silvia Fuselli Susanne Fritsch-Decker Takeshi Todo Carsten Weiss Daniela Vallone Tilman Lamparter Cristiano Bertolucci Nicholas S. Foulkes |
| author_facet | Hongxiang Li Carina Scheitle Giuseppe Di Mauro Silvia Fuselli Susanne Fritsch-Decker Takeshi Todo Carsten Weiss Daniela Vallone Tilman Lamparter Cristiano Bertolucci Nicholas S. Foulkes |
| author_sort | Hongxiang Li |
| collection | DOAJ |
| description | Abstract DNA damage is generated by various environmental stressors and so DNA repair systems must inevitably adapt to changing environments. Photolyases represent a highly conserved class of enzymes which repair UV-induced covalent crosslinks between adjacent pyrimidine bases (CPD and 6-4 photoproducts) via photoreactivation. In the blind cavefish Phreatichthys andruzzii which has evolved for millions of years completely isolated from UV radiation and visible light, we have documented multiple polymorphisms and loss of function mutations affecting both the 6-4phr and DASHphr photolyase genes while strangely, the CPDphr gene remains highly conserved. Using loss and gain of photolyase function medaka and mammalian cell lines, we reveal a novel function for CPDphr. Specifically, it enables the light-independent repair of CPD as well as 8-OHdG, an oxidatively modified form of guanosine which are both generated under oxidative stress in the absence of UV radiation. Thereby we document selective conservation of light-independent photolyase function in blind cavefish, enabling the repair of DNA damage encountered in an extreme subterranean environment. |
| format | Article |
| id | doaj-art-6da5543c09144f13b121a3bd4e8309ff |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6da5543c09144f13b121a3bd4e8309ff2025-08-20T03:05:06ZengNature PortfolioNature Communications2041-17232025-08-0116111310.1038/s41467-025-62795-7Conservation of dark CPD photolyase function in blind cavefishHongxiang Li0Carina Scheitle1Giuseppe Di Mauro2Silvia Fuselli3Susanne Fritsch-Decker4Takeshi Todo5Carsten Weiss6Daniela Vallone7Tilman Lamparter8Cristiano Bertolucci9Nicholas S. Foulkes10Institute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyInstitute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyInternational Centre for Genetic Engineering and BiotechnologyDepartment of Life Science and Biotechnology, University of FerraraInstitute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyRadioisotope Research Center, Institute for Radiation Science, Osaka UniversityInstitute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyInstitute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyBotanical Institute, Karlsruhe Institute of TechnologyDepartment of Life Science and Biotechnology, University of FerraraInstitute of Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of TechnologyAbstract DNA damage is generated by various environmental stressors and so DNA repair systems must inevitably adapt to changing environments. Photolyases represent a highly conserved class of enzymes which repair UV-induced covalent crosslinks between adjacent pyrimidine bases (CPD and 6-4 photoproducts) via photoreactivation. In the blind cavefish Phreatichthys andruzzii which has evolved for millions of years completely isolated from UV radiation and visible light, we have documented multiple polymorphisms and loss of function mutations affecting both the 6-4phr and DASHphr photolyase genes while strangely, the CPDphr gene remains highly conserved. Using loss and gain of photolyase function medaka and mammalian cell lines, we reveal a novel function for CPDphr. Specifically, it enables the light-independent repair of CPD as well as 8-OHdG, an oxidatively modified form of guanosine which are both generated under oxidative stress in the absence of UV radiation. Thereby we document selective conservation of light-independent photolyase function in blind cavefish, enabling the repair of DNA damage encountered in an extreme subterranean environment.https://doi.org/10.1038/s41467-025-62795-7 |
| spellingShingle | Hongxiang Li Carina Scheitle Giuseppe Di Mauro Silvia Fuselli Susanne Fritsch-Decker Takeshi Todo Carsten Weiss Daniela Vallone Tilman Lamparter Cristiano Bertolucci Nicholas S. Foulkes Conservation of dark CPD photolyase function in blind cavefish Nature Communications |
| title | Conservation of dark CPD photolyase function in blind cavefish |
| title_full | Conservation of dark CPD photolyase function in blind cavefish |
| title_fullStr | Conservation of dark CPD photolyase function in blind cavefish |
| title_full_unstemmed | Conservation of dark CPD photolyase function in blind cavefish |
| title_short | Conservation of dark CPD photolyase function in blind cavefish |
| title_sort | conservation of dark cpd photolyase function in blind cavefish |
| url | https://doi.org/10.1038/s41467-025-62795-7 |
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