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ATM specifically mediates repair of double-strand breaks with blocked DNA ends

 

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Opened Access ATM specifically mediates repair of double-strand breaks with blocked DNA ends
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Author: Álvarez Quilón, Alejandro
Serrano Benítez, Almudena
Ariel Lieberman, Jenna
Quintero, Cristina
Sánchez Gutiérrez, Daniel
Escudero Cuadrado, Luis María
Cortés Ledesma, Felipe
Department: Universidad de Sevilla. Departamento de Biología Celular
Date: 2014
Published in: Nature Communications, 5, 3347-1-3347-10.
Document type: Article
Abstract: Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked. We therefore identify the nature of ATM involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic trigger of ataxia telangiectasia and related disorders.
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URI: http://hdl.handle.net/11441/56529

DOI: http://dx.doi.org/10.1038/ncomms4347

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