%0 Journal Article
%A Baranes-Bachar, Keren
%A Levy-Barda, Adva
%A Oehler, Judith
%A Reid, Dylan A
%A Soria-Bretones, Isabel
%A Voss, Ty C
%A Chung, Dudley
%A Park, Yoon
%A Liu, Chao
%A Yoon, Jong-Bok
%A Li, Wei
%A Dellaire, Graham
%A Misteli, Tom
%A Huertas, Pablo
%A Rothenberg, Eli
%A Ramadan, Kristijan
%A Ziv, Yael
%A Shiloh, Yosef
%T The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair.
%D 2018
%U http://hdl.handle.net/10668/12204
%X 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 upregulation 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 the complex DDR network for accurate and balanced execution of DSB repair.
%K DNA damage
%K UBE4A
%K double-strand breaks
%K genome stability
%K ubiquitin
%~