A Mouse Model of ATR-Seckel Shows Embryonic Replicative Stress and Accelerated Aging

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Jul 22

PMID 19620979

Citations 193

Authors

Matilde Murga

Samuel Bunting

Maria F Montana

Rebeca Soria

Francisca Mulero

Marta Canamero

Youngsoo Lee

Peter J McKinnon

Andre Nussenzweig

Oscar Fernandez-Capetillo

Affiliations

Soon will be listed here.

Abstract

Although DNA damage is considered a driving force for aging, the nature of the damage that arises endogenously remains unclear. Replicative stress, a source of endogenous DNA damage, is prevented primarily by the ATR kinase. We have developed a mouse model of Seckel syndrome characterized by a severe deficiency in ATR. Seckel mice show high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice show accelerated aging, which is further aggravated in the absence of p53. Together, these results support a model whereby replicative stress, particularly in utero, contributes to the onset of aging in postnatal life, and this is balanced by the replicative stress-limiting role of the checkpoint proteins ATR and p53.

Citing Articles

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