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Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans.

Frohns, Florian ; Frohns, Antonia ; Kramer, Johanna ; Meurer, Katharina ; Rohrer-Bley, Carla ; Solovei, Irina ; Hicks, David ; Layer, Paul G. ; Löbrich, Markus (2020)
Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans.
In: Cells, 9 (4)
doi: 10.3390/cells9040947
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

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.

Typ des Eintrags: Artikel
Erschienen: 2020
Autor(en): Frohns, Florian ; Frohns, Antonia ; Kramer, Johanna ; Meurer, Katharina ; Rohrer-Bley, Carla ; Solovei, Irina ; Hicks, David ; Layer, Paul G. ; Löbrich, Markus
Art des Eintrags: Bibliographie
Titel: Differences in the Response to DNA Double-Strand Breaks between Rod Photoreceptors of Rodents, Pigs, and Humans.
Sprache: Englisch
Publikationsjahr: 12 April 2020
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Cells
Jahrgang/Volume einer Zeitschrift: 9
(Heft-)Nummer: 4
DOI: 10.3390/cells9040947
Kurzbeschreibung (Abstract):

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.

ID-Nummer: pmid:32290532
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Developmental Biology and Neurogenetics
10 Fachbereich Biologie > Radiation Biology and DNA Repair
Hinterlegungsdatum: 20 Apr 2020 11:37
Letzte Änderung: 20 Apr 2020 11:37
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