Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice. / Lopez-Contreras, Andres J; Specks, Julia; Barlow, Jacqueline H; Ambrogio, Chiara; Madsen, Claus Desler; Vikingsson, Svante; Rodrigo-Perez, Sara; Green, Henrik; Rasmussen, Lene Juel; Murga, Matilde; Nussenzweig, André; Fernandez-Capetillo, Oscar.
I: Genes & Development, Bind 29, Nr. 7, 01.04.2015, s. 690-5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice
AU - Lopez-Contreras, Andres J
AU - Specks, Julia
AU - Barlow, Jacqueline H
AU - Ambrogio, Chiara
AU - Madsen, Claus Desler
AU - Vikingsson, Svante
AU - Rodrigo-Perez, Sara
AU - Green, Henrik
AU - Rasmussen, Lene Juel
AU - Murga, Matilde
AU - Nussenzweig, André
AU - Fernandez-Capetillo, Oscar
N1 - © 2015 Lopez-Contreras et al.; Published by Cold Spring Harbor Laboratory Press.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
U2 - 10.1101/gad.256958.114
DO - 10.1101/gad.256958.114
M3 - Journal article
C2 - 25838540
VL - 29
SP - 690
EP - 695
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 7
ER -
ID: 135739326