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

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.

authors

Meira LB,Moroski-Erkul CA,Green SL,Calvo JA,Bronson RT,Shah D,Samson LD

doi

10.1073/pnas.0807030106

subject

Has Abstract

pub_date

2009-01-20 00:00:00

pages

888-93

issue

3

eissn

0027-8424

issn

1091-6490

pii

0807030106

journal_volume

106

pub_type

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