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

Lisiane B. Meira; Catherine A. Moroski-Erkul; Stephanie L. Green; Jennifer A. Calvo; Roderick T. Bronson; Dharini Shah; Leona D. Samson

doi:10.1073/pnas.0807030106

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

Lisiane B. Meira, Catherine A. Moroski-Erkul, Stephanie L. Green, Jennifer A. Calvo, Roderick T. Bronson, Dharini Shah, Leona D. Samson

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

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.

Original language	English
Pages (from-to)	888-893
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	106
Issue number	3
DOIs	https://doi.org/10.1073/pnas.0807030106
State	Published - 20 Jan 2009
Externally published	Yes

Keywords

Alkylation damage
Apoptosis
DNA glycosylase
Photoreceptors

Access to Document

10.1073/pnas.0807030106

Cite this

@article{2dd0a74e70b945c6936e3d485a7e5d2c,

title = "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.",

keywords = "Alkylation damage, Apoptosis, DNA glycosylase, Photoreceptors",

author = "Meira, {Lisiane B.} and Moroski-Erkul, {Catherine A.} and Green, {Stephanie L.} and Calvo, {Jennifer A.} and Bronson, {Roderick T.} and Dharini Shah and Samson, {Leona D.}",

year = "2009",

month = jan,

day = "20",

doi = "10.1073/pnas.0807030106",

language = "English",

volume = "106",

pages = "888--893",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "3",

}

TY - JOUR

T1 - Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice

AU - Meira, Lisiane B.

AU - Moroski-Erkul, Catherine A.

AU - Green, Stephanie L.

AU - Calvo, Jennifer A.

AU - Bronson, Roderick T.

AU - Shah, Dharini

AU - Samson, Leona D.

PY - 2009/1/20

Y1 - 2009/1/20

N2 - 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.

AB - 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.

KW - Alkylation damage

KW - Apoptosis

KW - DNA glycosylase

KW - Photoreceptors

UR - http://www.scopus.com/inward/record.url?scp=58849095932&partnerID=8YFLogxK

U2 - 10.1073/pnas.0807030106

DO - 10.1073/pnas.0807030106

M3 - Article

C2 - 19139400

AN - SCOPUS:58849095932

SN - 0027-8424

VL - 106

SP - 888

EP - 893

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 3

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this