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 Devjournal_title
Genes & developmentauthors
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 Odoi
10.1101/gad.256958.114subject
Has Abstractpub_date
2015-04-01 00:00:00pages
690-5issue
7eissn
0890-9369issn
1549-5477pii
gad.256958.114journal_volume
29pub_type
杂志文章abstract::The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...
journal_title:Genes & development
pub_type: 杂志文章
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abstract::The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...
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journal_title:Genes & development
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abstract::A conditional block to transcriptional elongation is an important mechanism for regulating c-myc gene expression. This elongation block within the first c-myc exon was defined originally in mammalian cells by nuclear run-on transcription analyses. Subsequent oocyte injection and in vitro transcription analyses suggest...
journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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abstract::During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At...
journal_title:Genes & development
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doi:
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2017-06-15 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2008-01-15 00:00:00
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journal_title:Genes & development
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