Ctf4 Prevents Genome Rearrangements by Suppressing DNA Double-Strand Break Formation and Its End Resection at Arrested Replication Forks.
Mol Cell
; 66(4): 533-545.e5, 2017 May 18.
Article
em En
| MEDLINE
| ID: mdl-28525744
ABSTRACT
Arrested replication forks lead to DNA double-strand breaks (DSBs), which are a major source of genome rearrangements. Yet DSB repair in the context of broken forks remains poorly understood. Here we demonstrate that DSBs that are formed at arrested forks in the budding yeast ribosomal RNA gene (rDNA) locus are normally repaired by pathways dependent on the Mre11-Rad50-Xrs2 complex but independent of HR. HR is also dispensable for DSB repair at stalled forks at tRNA genes. In contrast, in cells lacking the core replisome component Ctf4, DSBs are formed more frequently, and these DSBs undergo end resection and HR-mediated repair that is prone to rDNA hyper-amplification; this highlights Ctf4 as a key regulator of DSB end resection at arrested forks. End resection also occurs during physiological rDNA amplification even in the presence of Ctf4. Suppression of end resection is thus important for protecting DSBs at arrested forks from chromosome rearrangements.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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DNA Fúngico
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Rearranjo Gênico
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Origem de Replicação
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Proteínas de Saccharomyces cerevisiae
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Proteínas de Ligação a DNA
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Reparo do DNA
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Replicação do DNA
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Quebras de DNA de Cadeia Dupla
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão