Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

Proceedings of the National Academy of Sciences of the United States of America
L B MeiraLeona D Samson

Abstract

Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

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Citations

Nov 4, 2011·Chromosoma·Angelika L Jacobs, Primo Schär
Jan 13, 2012·Nature Reviews. Cancer·Dragony FuLeona D Samson
Jul 16, 2010·The Journal of Biological Chemistry·Michael W SchmittLawrence A Loeb
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Apr 18, 2013·PLoS Genetics·Jennifer A CalvoLeona D Samson
Dec 4, 2012·International Journal of Molecular Sciences·Matthias BosshardBarbara van Loon
Oct 25, 2012·Journal of Oncology·Rita RosatiDiane C Cabelof
Jul 6, 2014·DNA Repair·Lisiane B MeiraLeona D Samson
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Nov 10, 2012·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·Z M ZaïrG J Jenkins
Jul 2, 2014·The Journal of Cell Biology·Michael EnsmingerMarkus Lӧbrich
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mohammad R EbrahimkhaniLeona D Samson
Aug 9, 2011·Mechanisms of Ageing and Development·Lene Juel RasmussenVilhelm A Bohr
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Aug 9, 2021·DNA Repair·Jing GeBevin P Engelward
Jun 2, 2021·Annual Review of Vision Science·Laura CampelloAnand Swaroop
Sep 17, 2021·Scientific Reports·Yong LiWioletta Czaja

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