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- Zhao, Haiyu, et al.
(författare)
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Modulation of DNA Repair Systems in Blind Cavefish during Evolution in Constant Darkness
- 2018
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 28:20, s. 3229-3243
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Tidskriftsartikel (refereegranskat)abstract
- How the environment shapes the function and evolution of DNA repair systems is poorly understood. In a comparative study using zebrafish and the Somalian blind cavefish, Phreatichthys andruzzii, we reveal that during evolution for millions of years in continuous darkness, photoreactivation DNA repair function has been lost in P. andruzzii. We demonstrate that this loss results in part from loss-of-function mutations in pivotal DNA-repair genes. Specifically, C-terminal truncations in P. andruzzii DASH and 6-4 photolyase render these proteins predominantly cytoplasmic, with consequent loss in their functionality. In addition, we reveal a general absence of light-, UV-, and ROS-induced expression of P. andruzzii DNA-repair genes. This results from a loss of function of the D-box enhancer element, which coordinates and enhances DNA repair in response to sunlight. Our results point to P. andruzzii being the only species described, apart from placental mammals, that lacks the highly evolutionary conserved photoreactivation function. We predict that in the DNA repair systems of P. andruzzii, we may be witnessing the first stages in a process that previously occurred in the ancestors of placental mammals during the Mesozoic era.
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| 3. |
- Zhao, Haiyu, et al.
(författare)
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Regulation of ddb2 expression in blind cavefish and zebrafish reveals plasticity in the control of sunlight-induced DNA damage repair
- 2021
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Ingår i: PLOS GENETICS. - : Public Library of Science (PLoS). - 1553-7404. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- We have gained considerable insight into the mechanisms which recognize and repair DNA damage, but how they adapt to extreme environmental challenges remains poorly understood. Cavefish have proven to be fascinating models for exploring the evolution of DNA repair in the complete absence of UV-induced DNA damage and light. We have previously revealed that the Somalian cavefish Phreatichthys andruzzii, lacks photoreactivation repair via the loss of light, UV and ROS-induced photolyase gene transcription mediated by D-box enhancer elements. Here, we explore whether other systems repairing UV-induced DNA damage have been similarly affected in this cavefish model. By performing a comparative study using P. andruzzii and the surface-dwelling zebrafish, we provide evidence for a conservation of sunlight-regulated Nucleotide Excision Repair (NER). Specifically, the expression of the ddb2 gene which encodes a key NER recognition factor is robustly induced following exposure to light, UV and oxidative stress in both species. As in the case of the photolyase genes, D-boxes in the ddb2 promoter are sufficient to induce transcription in zebrafish. Interestingly, despite the loss of D-box-regulated photolyase gene expression in P. andruzzii, the D-box is required for ddb2 induction by visible light and oxidative stress in cavefish. However, in the cavefish ddb2 gene this D-box-mediated induction requires cooperation with an adjacent, highly conserved E2F element. Furthermore, while in zebrafish UV-induced ddb2 expression results from transcriptional activation accompanied by stabilization of the ddb2 mRNA, in P. andruzzii UV induces ddb2 expression exclusively via an increase in mRNA stability. Thus, we reveal plasticity in the transcriptional and post transcriptional mechanisms regulating the repair of sunlight-induced DNA damage under long-term environmental challenges.Author summaryThe integrity of genetic information is frequently challenged by environmental factors such as sunlight which induce mutations in DNA. Therefore, DNA damage repair mechanisms are ubiquitous and highly conserved. While significant progress has been made in understanding how these mechanisms recognize and repair DNA damage, how they adapt to long-term environmental challenges remains poorly understood. Cavefish have proven to be fascinating models for exploring the function of DNA repair systems in extreme photic environments. We have previously shown that during evolution for millions of years in complete isolation from sunlight, the Somalian cavefish, Phreatichthys andruzzii has lost photoreactivation, a ubiquitous, light-dependent DNA repair system. This results in part from a loss of light, UV and ROS-induced gene transcription. Have other repair systems targeting UV-induced DNA damage been affected in cavefish? Here, we provide evidence that Nucleotide Excision Repair (NER) function is retained in cavefish and is upregulated upon sunlight exposure. Furthermore, we reveal complexity in the transcriptional and posttranscriptional mechanisms regulating the repair of UV-induced DNA damage.
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