{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:17:38Z","timestamp":1790468258620,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T00:00:00Z","timestamp":1586649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["02NUK034A"],"award-info":[{"award-number":["02NUK034A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK 1657"],"award-info":[{"award-number":["GRK 1657"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pro Retina Deutschland Foundation","award":["Projekt 55200390"],"award-info":[{"award-number":["Projekt 55200390"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Genome editing (GE) represents a powerful approach to fight inherited blinding diseases in which the underlying mutations cause the degeneration of the light sensing photoreceptor cells of the retina. Successful GE requires the efficient repair of DNA double-stranded breaks (DSBs) generated during the treatment. Rod photoreceptors of adult mice have a highly specialized chromatin organization, do not efficiently express a variety of DSB response genes and repair DSBs very inefficiently. The DSB repair efficiency in rods of other species including humans is unknown. Here, we used ionizing radiation to analyze the DSB response in rods of various nocturnal and diurnal species, including genetically modified mice, pigs, and humans. We show that the inefficient repair of DSBs in adult mouse rods does not result from their specialized chromatin organization. Instead, the DSB repair efficiency in rods correlates with the level of Kruppel-associated protein-1 (KAP1) expression and its ataxia-telangiectasia mutated (ATM)-dependent phosphorylation. Strikingly, we detected robust KAP1 expression and phosphorylation only in human rods but not in rods of other diurnal species including pigs. Hence, our study provides important information about the uniqueness of the DSB response in human rods which needs to be considered when choosing model systems for the development of GE strategies.<\/jats:p>","DOI":"10.3390\/cells9040947","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T03:10:01Z","timestamp":1586833801000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans"],"prefix":"10.3390","volume":"9","author":[{"given":"Florian","family":"Frohns","sequence":"first","affiliation":[{"name":"Radiation Biology and DNA Repair, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Frohns","sequence":"additional","affiliation":[{"name":"Plant Membrane Biophysics, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Kramer","sequence":"additional","affiliation":[{"name":"Developmental Biology and Neurogenetics, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Meurer","sequence":"additional","affiliation":[{"name":"Radiation Biology and DNA Repair, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-2722","authenticated-orcid":false,"given":"Carla","family":"Rohrer-Bley","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, CH-8057 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6813-7279","authenticated-orcid":false,"given":"Irina","family":"Solovei","sequence":"additional","affiliation":[{"name":"Biozentrum, Biology-II, University of Munich (LMU), 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hicks","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Int\u00e9gratives, Universit\u00e9 de Strasbourg, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Layer","sequence":"additional","affiliation":[{"name":"Developmental Biology and Neurogenetics, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"L\u00f6brich","sequence":"additional","affiliation":[{"name":"Radiation Biology and DNA Repair, Technical University of Darmstadt, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/aos.13141","article-title":"A review of the mechanisms of cone degeneration in retinitis pigmentosa","volume":"8","author":"Narayan","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ymeth.2014.03.026","article-title":"Genome engineering with TALENs and ZFNs: Repair pathways and donor design","volume":"69","author":"Carroll","year":"2014","journal-title":"Methods"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Peddle, C.F., Fry, L.E., McClements, M.E., and MacLaren, R.E. 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