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The ubiquitin E3/E4 ligase, UBE4A, fine-tunes protein ubiquitylation and accumulation at sites of DNA damage facilitating double-strand break repair

 

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Opened Access The ubiquitin E3/E4 ligase, UBE4A, fine-tunes protein ubiquitylation and accumulation at sites of DNA damage facilitating double-strand break repair
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Author: Soria Bretones, Isabel
Baranes Bachar, Keren
Huertas Sánchez, Pablo
Levy Barda, Adva
Oehler, Judith
Department: Universidad de Sevilla. Departamento de Genética
Date: 2018
Published in: Molecular Cell, 69 (5), 866-878.
Document type: Article
Abstract: Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning - the E3/E4 ubiquitin ligase, UBE4A. UBE4A’s recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites. This pathway is essential for optimal end-resection at DSBs, and its abrogation leads to up-regulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair. Our data uncover a critical regulatory level in the DSB response and underscore the importance of fine-tuning of the complex DDR network for accurate and balanced execution of DSB repair
Cite: Soria Bretones, I., Baranes Bachar, K., Huertas Sánchez, P., Levy Barda, A. y Oehler, J. (2018). The ubiquitin E3/E4 ligase, UBE4A, fine-tunes protein ubiquitylation and accumulation at sites of DNA damage facilitating double-strand break repair. Molecular Cell, 69 (5), 866-878.
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URI: https://hdl.handle.net/11441/84468

DOI: 10.1016/j.molcel.2018.02.002

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