Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.

Abstract:

:In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.

journal_name

Genes Dev

journal_title

Genes & development

authors

Lopez-Contreras AJ,Specks J,Barlow JH,Ambrogio C,Desler C,Vikingsson S,Rodrigo-Perez S,Green H,Rasmussen LJ,Murga M,Nussenzweig A,Fernandez-Capetillo O

doi

10.1101/gad.256958.114

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

690-5

issue

7

eissn

0890-9369

issn

1549-5477

pii

gad.256958.114

journal_volume

29

pub_type

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